Gastrointestinal stromal tumor: A type of tumor that usually begins in cells in the wall of the gastrointestinal tract. It can be benign or malignant. Abbreviated GIST. Malignant GISTs can occur from the esophagus to the rectum, but occur most commonly in the stomach and small intestine. Treatment for GIST includes STI571 (Gleevec), the first approved drug to directly turn off the signal of a protein known to cause a cancer.