This research describes the significance of Lennie Small, a character from John Steinbeck’s Of Mice and Men novel, to both Steinbeck’s novel and Robert Burns’ poem entitled To a Mouse. This research belongs to descriptive qualitative study which analyses the novel as the primary source of study. In analyzing the novel, I used C.S. Peirce’s iconicity as the approach to identify Lennie’s characteristics and significance in the novel. Furthermore, I applied Michael Riffaterre’s textual interpretant to find out the relation between Steinbeck’s Of Mice and Men novel and Burns’ To a Mouse poem. The result shows that Lennie’s symbolizes the character referred as Mouse in Burns’ poem. From this study, I learned that mentally handicapped people like Lennie might suffer the same fate like the Mouse in Burns’ poem; unaccepted, isolated, and tortured by the society.