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The title of "Of Mice and Men" is an allusion taken from a poem by the Scottish poet, Robert Burns. The line of the poem from which the title is taken says, "The best laid plan o'mice and men gang oft agley." In plain English, Burns is saying the no matter how well we plan things, often things turn out differently the we planned. This is a reference to the dreams of the farm that Lennie and George share. Just as that dream is about to come true, the dream is shattered by Lennie when he kills Curley's wife. To prevent Lennie from suffering horrible treatment at the hands of the men and Curley, George kills Lennie and their dream dies. The title is a direct allusion to the theme and the ending of the novel.
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