* ActingForTwo: Alex Ivanovici voices Lorenzo de' Medici, Bartolomeo d'Alviano and Girolamo Savonarola in English.
* CrossRegionalVoiceActing: This game, like the rest of the series, uses a mix of Montreal and Los Angeles voice actors, accompanied by Italian actors.
* FakeNationality: While a good chunk of the cast are actually Italians, some were certainly not from the country or have Italian ancestry.
** A good example is the decidedly non-Italian and American Creator/RogerCraigSmith, the voice actor of Ezio Auditore.
** Ditto the Egyptian-born (of Lebanese descent) French-speaking Canadian Creator/ManuelTadros as the Spanish-born Italian Rodrigo Borgia.
* MultipleLanguagesSameVoiceActor: Creator/ManuelTadros voices Rodrigo Borgia/Pope Alexander VI in both English and French.
* PlayingAgainstType: In the Japanese version, Creator/AyakoKawasumi and Creator/KaoriNazuka are normally typecasted in {{Anime}} voicing heroic or kinder roles. In this game, both actresses voiced two of the ''most cruelest women of the Renaissance'': Lucrezia Borgia and Caterina Sforza, respectively.
* WhatCouldHaveBeen: Rosa would've made future appearances in the franchise had her voice actress, Lita Tresierra, not been [[CharacterOutlivesActor tragically killed in a car accident]].
* YouSoundFamiliar: In the French version, Creator/MarcAlfos voiced both Mario Auditore and Richard the Lionheart in the [[VideoGame/AssassinsCreedI first game]].
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