Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the digestive tract. They are relatively rare neoplasms compared with gastrointestinal carcinomas and usually can readily be differentiated from carcinomas based on the morphology of the neoplastic cells that are typically spindled (70%), pure epithelioid, or mixed type. GISTs in general lack expression of cytokeratin and exhibit immunoreactivity toward CD117, CD34, or DOG1. GISTs can demonstrate a pure epithelioid morphology that can appear similar histologically to a carcinoma. Very few epithelioid GISTs have been reported to express cytokeratin, which can lead to diagnostic challenges especially in cases with pure epithelioid morphology. Epithelioid GISTs should be considered in the differential diagnosis when evaluating gastrointestinal neoplasms with overlapping epithelioid and carcinoma-like morphology. An accurate diagnosis can be made using additional immunohistochemical studies directed against CD117, CD34, or DOG1. Advanced investigations such as mutation analysis of KIT using molecular pathology methods can further assist in confirming the diagnosis.