Gastrointestinal stromal tumor (GIST), generally driven by oncogenic KIT or PDGFRA mutations, is the most common mesenchymal tumor of the gastrointestinal (GI) tract. GIST is most common in the stomach (60%) and small intestine (30%), but can occur anywhere in the GI-tract and the intra-abdominal soft tissues. GIST can show spindle cell or epithelioid morphology, and mitotic count and tumor size are most important prognostic parameters. GISTs in NF1 patients and children are distinctive clinicopathologic groups. Immunohistochemical testing for KIT and sometimes for DOG1/Ano 1 is essential in confirming the diagnosis. J. Surg. Oncol. 2011; 104:865–873. © 2011 Wiley Periodicals, Inc.