Gastrointestinal stromal tumor (GISTs) are the most common connective tissue malignancies of the gastrointestinal (GI) tract, with an incidence on the order of 10-13 per million people per year. Primary therapy is usually surgical, but the recurrence rate of large, so-called high-risk tumors, with a high mitotic rate, or those arising from small bowel and colon/rectum is particularly high. The natural history, pathology, and molecular biology of GISTs are discussed in this review, as are features of increasing our analytical power of the genes altered in these tumors, surgical issues, and the translation of research findings into clinical practice. The biological features of GIST make it a model for the examination of kinase-targeted therapeutics in solid tumors.
