Mitotic activity and tumor size are currently regarded as the most powerful prognostic indicators for patients with gastrointestinal stromal tumor (GIST). This retrospective study evaluated the prognostic accuracy of MIB-1 proliferative index (PI) in combination with these two indicators in 35 GIST patients. Within a high-risk group, determined initially by tumor size and mitotic count, overall survival was significantly shorter for patients whose tumors had PI > or = 10% MIB-1 positive cells. When tumor location (gastric versus small intestine) was taken into account, a combination of tumor size, mitotic count, and PI > or = 10% identified a subgroup of patients with significantly shorter survival for gastric (but not small intestinal) GIST. Based on our results, MIB-1 immunostaining, when used in combination with tumor size and mitotic count, appears to be a powerful tool for identifying patients, especially those with gastric tumors, at high risk of recurrence and early tumor-related death