- When Carlson shoots Candy's dog so he wouldn't have to suffer anymore. This foreshadows what happens to Lennie and George's friendship near the end of the story.
- The "Guys like us" speech. Heart-warming at first, but the reprise is cruel. Especially: "But not like us. Because—" "Because I got you an'—" "An' I got you." "And I get to tend the rabbits." It's even crueller when it's said right before George shoots Lennie.
- The final three pages are what truly take the cake, though. And as the book is now considered Public Domain, enjoy.And George raised the gun and steadied it, and he brought the muzzle of it close to the back of Lennie's head. The hand shook violently, but his face set and his hand steadied. He pulled the trigger. The crash of the shot rolled up the hills and rolled down again. Lennie jarred, and then settled slowly forward to the sand, and he lay without quivering.
- One particularly tragic moment in a scene full of them is near the end where Lennie reveals that he has memorised George's rants at what a burden he is as well as his hopeful speech about the farm. George can only exclaim "You can't remember nothing that happens, but you remember every word I say" while Lennie continues his Oblivious Guilt Slinging as he brings up all the other mean-spirited things George has said in his fits of frustration. Lennie urges him to continue with the angry monologue, showing that he really does treat every word out of George's mouth as gospel, and is almost as reverential of George's moments of bile as he is of his affection.
Tear Jerker / Of Mice & Men