Spindle cell lesions of the gastrointestinal tract are relatively uncommon compared with the frequency of their epithelial counterparts. Although gastrointestinal stromal tumors and leiomyomas are the most commonly encountered spindle cell lesions in the stomach and esophagus, respectively, there are other less common diagnostic entities that should be considered for accurate diagnoses as well as appropriate patient treatment and clinical follow-up. Given the morphologic overlap of low-grade spindle cell lesions on cytologic preparations, ancillary studies play a key role in differentiating these lesions from one another.