Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. GIST have characteristic morphological features and are positive for KIT (CD117). Overexpression of KIT in the tumor cells results from constitutive activation of the KIT tyrosine kinase receptor. KIT activation leads to intracellular signaling that causes increased cellular proliferation and enhanced cell survival leading to tumor formation. A successful therapeutic strategy is available with the pharmacological agent SCI.-571 that blocks the intracellular effects of KIT activation. GIST are more common in the stomach (60-70%) and the small intestine (25-35%), with a minority of lesions occurring in the colon, rectum, appendix and esophagus. GIST differ histologically, immunohistochemically and genetically from leiomyomas, leiomyosarcomas and schwannomas. The pathologist plays an important role in the evaluation of these lesions. Adequate gross and microscopic pathological evaluation are crucial in the determination of treatment and prognosis.