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- In Descendants of Darkness, gate keepers can be identified by their different colored eyes. Wakaba has an orange right eye and a brown left eye.
- Neko from K has a green right eye and blue left eye in her human form, which makes her look far from normal. She's not, of course, and is quickly identified as a Strain, an individual with supernatural powers that were not given by a King. Her specialty is creating illusions and modifying the memories of the people around her with her presence.
- In the manga Enchanter by Izumi Kawachi, if you become an enchanter, one of your eyes changes, turning deep red with a pinpoint pupil. Oddly, long-time friends don't seem to notice the change.
- In Tengen Toppa Gurren Lagann, Lordgenome has spiral eyes, to signify his status as a user of Spiral power. Kittan also develops these eye spirals just before he dies, and Simon has just one in the Distant Finale.
- In Yona of the Dawn, out of the Four Dragons, Kija and Shin-Ah possess more noticeable physical traits, excluding the hair colors. Kija's right hand is a dragon claw and Shin-Ah's eyes are not only stunning but also have red markings underneath them.
- In Tokyo Ghoul, Kaneki and all other One-Eyed Ghouls only have a single Kakugan. This immediately marks them as different from regular Ghouls, but also not fully human. Some are able to control it, while others have one that is permanently active.
- Wolf's Rain: Darcia's left eye is a wolf's eye. He can turn into a large black (possibly dire?) wolf because his family is descended from wolves that wanted to be fully human.
- In InuYasha, the half-demons look very human, but their skin, hair and eyes often have unusual colors. Many of them also have animal or demonic characteristics on their bodies.
- In Claymore the female warriors are half yoma and half human, with silver eyes and light blonde or even white hair. Some of them also have pointed ears, like elves.
- The principal rival to Josie James in Archie Comics' She's Josie series is Alexandra Cabot, who is an unremarkable bobbed brunette with witchcraft powers. When the characters were adapted by Hanna-Barbera Studios into Josie And The Pussy Cats in 1970, Alexandra was remodeled into a raven ponytail with a distinctive white Skunk Stripe; however, the cartoon Alexandra has no magical powers. The success of the cartoon show compelled Archie Comics to Retcon their Josie characters, resulting in the current Alexandra having the distinctive Skunk Stripe and witchcraft powers.
- In Empath: The Luckiest Smurf, the main character, who is a telepath and telekinetic, has a yellow star mark on his forehead to indicate this. All Psyches also bear this mark on their foreheads.
- In 28 Weeks Later, the mother and her son have heterochromia. When she becomes a vector for The Virus, it serves as a clue to her and her son's shared biological resistance to the virus, and an indicator of when they become exposed but remain unturned: one eye becomes bloodshot like a normal zombie's infected would, the other remains clear.
- The strange white cat in Mountolive's mansion in The Legacy has differently colored eyes, which is a first hint that it is actually a shapeshifter.
- All sorcerers in The Belgariad have a distinctive white mark somewhere on their body. Polgara's is a white lock of hair, while Garion and his ancestors all have a white circle on their palms, indicative of their connection with the Orb of Aldur.
- In Kristin Cashore's Graceling, all "Gracelings" have this as a distinguishing characteristic. It becomes important to the plot when you find out that one of the kings is missing an eye, and it later turns out that he is Graced with a very effective version of Charm Person, as it can work even second- and third-hand, via rumors.
- A Song of Ice and Fire:
- Euron "Crow's Eye" Greyjoy hides a black eye behind an eye patch. His other one, called his smiling eye, is blue. There's an implied connection between his eyes and his magic.
- Minor character Shiera Seastar has one blue eye and one green eye, supposedly due, in part, to her rumoured black magic.
- In the Roger Zelazny book This Immortal, protagonist narrator Conrad Nomikos has heterochromia, among other odd features. But then he is probably a mutant and is definitely hundreds of years old. His unique appearance is an important plot point.
- Farideh, heroine of Brimstone Angels, has one silver eye and one gold eye and her twin sister Havilar has two gold eyes because they are tieflings (humanoids with devil ancestry).
- In Terminal World, all tectomancers have a large red birthmark in the shape of a six-pointed star on the back of their heads.
- The main character of Ann Downer's Spellkey Trilogy has one green eye and one blue (which is a sign of magical power in that world).
- In The Mortal Instruments, warlocks have a distinguishing mark that's unique to each one. Magnus Bane has cat eyes, Catarina Loss has blue skin and white hair, and Ragnor Fell has ram horns, green skin and an extra joint in each finger. In the spinoff The Infernal Devices, Tessa, despite being a warlock, does not have a mark because her mother was a Shadowhunter. This is basically her distinguishing mark.
- In The Half Life Trilogy, witches have “glints” in their eyes.
- Journey to Chaos: If you see someone with Pointed Ears, then they are related, in some way, to chaotic energy and/or trickster gods.
- In A Darker Shade Of Magic, all Antari have one pitch-black eye.
- In The Shattered Kingdoms, Meiran/Lahlil's mismatched eyes are a consequence of her magical illness, which originates from having been "blessed" by both Nomas deities instead of just one. Both eyes still work, but not when she uses both at once, so she uses an eyepatch. In conjunction with other unusual features (Norlanders are generally considered to look corpse-like anyway, and she has a mess of non-supernatural burn marks on her forearm) she is quite distinctive in her appearance.
- In Wings of Fire, NightWings with actual mind-reading powers have a silver scale under each eye.
- In the world of Marus, as depicted in Adventures in Odyssey's Passages tie-in episode, different-colored eyes are recognized as a sign of prophecy. Interworldly interloper Alice physically goes from having brown eyes to blue and green, then loses them again when her time as The Unseen One's messenger is up.
- Dungeons & Dragons: This is an iconic trait that defines the "Planetouched", who first appeared in 2e's Planescape setting. Be they Aasimar (Celestial ancestor), Genasi (Elemental ancestor), Tiefling (Fiendish ancestor), or any of the other varieties, they always have markings that reflect their ancestry. Exactly how marked they are varies hugely from individual to individual; aasimars are usually more subtly marked than tieflings, but even the humanlike ones generally have at least one identifying mark that belies this. An aasimar descended from a solar frequently has vestigial feather patches at the shoulder blades, and one descended from a celestial serving a deity may have a birthmark in the shape of that god's holy symbol.
- Pathfinder gives extreme amounts of variation with its "Blood of Angels" and "Blood of Fiends" sourcebooks, which include sizable 2e-esque random trait lists and fully detailed explanations of traits typical to aasimar who strongly connect to their celestial ancestor.
- In the Eberron campaign setting the Dragonmarked manifest vibrant blue-and-white Draconic sigils somewhere on their skin when their spell-like abilities appear.
- Wraith: The Oblivion: While all wraiths are supernatural by definition, those wraiths who specialise in one of their magical arts (Arcanoi) generally develop markings that identify them as a practitioner - black eyes (Argos), stained black fingers (Castigate), never closing their eyes (Lifeweb), etc.
- In Sorcerer, the Telltale is a specific attribute that gives a sorcerer or a human-looking demon away to those in the know.
- In the Command & Conquer Tiberian series, people who have survived Tiberium exposure and have become mutated have green Tiberium crystals embedded in their bodies. They are often referred to as "shiners" because of the way the crystals glow.
- MapleStory's Luminous starts his story off with two blue eyes, then one of his eyes turns red when he absorbs the Black Mage's energy.
- In the Soul Series, Zasalamel has one normal-colored eye and one golden eye, possibly as a result of his immortality curse.
- In Ragnarok Online, the pope of Arunafeltz and her twin brother have opposite-color heterochromia. Apparently, this was one of the reasons she was chosen as pope. The other reasons was her hair and skin color.
- In the original Fable, the most magically powerful characters gain Prophet Eyes and glowing patterns under their skin. The wizard Maze has had his develop to the point of Volcanic Veins.
- In Fire Emblem Awakening, the royal family of Yllise has the Mark of Naga on their bodies, distinguishing them as the wielders of the legendary sword Falchion and who can awaken its power via the Awakening ritual. Chrom has the mark on his shoulder, while Emmeryn has it on her forehead. Lucina, Chrom's daughter, inherits the mark as well, which is located in the iris of her left eye.
- Link, Zelda, and Ganondorf from The Legend of Zelda each hold a piece of the Triforce. Link's is Courage (the lower right triangle), Zelda's is Wisdom (the lower left triangle), and Ganondorf's is Power (the top triangle). It shows up on the backs of their hands.
- In Dishonored, any person empowered by the Outsider gets a tattoo with its symbol on the back of one of their hands. It glows everytime they use their powers.
- In Dark Souls, the Undead are all branded by the "Dark Sign", a small, circular mark with what appear to be tiny flames coming off of it. Where the Dark Sign came from and why it exists are some of the driving questions of the series: it appears to be a force of nature. Undead afflicted by it do not turn evil... most of them are just regular folk; good people, bad people, stupid people, etc. However, as time goes on, and they "die" more and more, they gradually lose their minds, until they become "Hollow", a state in which the Undead has lost all humanity and reason, and mindlessly attacks anything that comes near. There is no known cure for it, though many in the series search for one.
- Dark Souls III finally gives us an answer on where the Darksign came from in The Ringed City; it was created by Lord Gwyn as a "seal of fire" meant to deny mankind of their innate access to the power of the Abyss and the Dark Soul. Thus cut off from that which makes them what they are, the dark began manifesting itself as the Undead curse in those with little Humanity, and as an all-consuming power that drives those possessed by it stark raving insane for those with too much, and the lack of control over their souls compared to bearers of light souls only made the problem worse for mankind.
- In Kult: Heretic Kingdoms, some children are born with scars known as the Mark of the Dead God, which generally indicate a high degree of magical ability. Alita, the protagonist, is such a person.
- Among the Cubi of Dan and Mab's Furry Adventures , one reclusive, mysterious clan all have different-coloured eyes, along with wings that are both feathered and leathery. The trait can appear in other clans, and is regarded as a good omen. Since Cubi can shapeshift, this applies only to their default forms. Abel, a central character, has both traits, and his father considers them important to his plans.
- In Doomsday My Dear the main character has one blue and one green eye because this is a trait of a carrier of the Blood Plague. Several other characters turn out to have this undesirable trait as the comic progresses.
- In Penny Blackfeather, the Adventurer has mismatched brown and blue eyes, with the blue eye appearing in color even in the Deliberately Monochrome parts of the comic (that is, everywhere outside of the Goblin Valley). Similarily, the magical parrot Princess is blue and so is the magicked-up Adventurer - it seems blue is the colour of magic in this world.
- All the Ravens (servants of the Raven) in Archipelago are inflicted with a left eye with a black sclera and a glowing red pupil, regardless of species. At least some of them can hide this to pass in normal society.
- Eyes are commonly used for this in The Sanity Circus. Fletch's are mismatched, one being black with a gold iris (shapeshifter residue from turning into a seagull frequently), and Sammy Talbot's have two pupils and a doubled iris in each.
- Several human SCP items from the SCP Foundation have these.
- SCP-073 has a mark on his forehead of unknown origin and Artificial Limbs (specifically arms, legs, shoulder blades and spinal chord).
- SCP-040 has pink hair and a Black Eye Of Crazy (although she herself isn't crazy).
- SCP-134 has pitch black eyes (which actually act as windows to another point in space).
- SCP-076-2 has tattoos all over him of occult iconography.
- SCP-239 has her radiation emitting grey eyes.
- In Polyhistor Academy, the Thrice-Cursed all possess an obviously magical deformity/mutation, that grants them a magical ability, and is usually blatantly obvious.
- On Futurama the only outward physical difference between alien Leela and all the humans is she only has one eye. Subverted later though, as we learn that she's not an alien - she's just a mutant. Since mutants are an oppressed minority and aliens aren't, her parents left her as a Doorstop Baby at an orphanarium, leaving a note saying she was alien in order for her to have a better life.
- Avatar: The Last Airbender: After Zhao kills the Moon Spirit, Tui, Yue becomes despondent believing there's no longer any hope for her people. However, Iroh takes note of her hair color and recognizes its significance.
Iroh: (in realization) "You...! You have been touched by the Moon Spirit!"
- Alicorns in My Little Pony: Friendship Is Magic possess both the wings of a pegasus and the horn of a unicorn, as well as whatever vaguely defined traits an earth pony has, just in the name of species equality. Possessing the traits of all three kinds of ponies makes them stand out as a Master of All. They also are Large and in Charge, with Celestia in particular towering over ordinary ponies - and even Twilight, who was originally the size of any other pony, appears to be growing. Luna and Celestia also possess magical sparkling manes which flow on their own, with Luna's looking like a starry night sky.