Gastrointestinal stromal tumors (GISTs) are c-KIT-signaling-driven mesenchymal tumors of the human digestive tract, many of which have c-KIT or PDGFRα activating mutations. The authors studied the immunohistochemical markers, c-KIT and PDGFRα mutations, in GISTs and their association with the clinicopathological and clinical follow-up in 145 GISTs. Tumors were located mainly in the stomach, the median tumor size being 7.5 cm. The mitotic index was ≤5 mitoses per 50 high-power fields in 61% of cases, 96% expressed CD117, and c-KIT or PDGFRα mutations were detected in 68% of cases. The median follow-up of the series was 52 months (range = 1 to 244.9 months). Tumor size, cell morphology, mitotic index, incomplete resection, Fletcher's risk classification, Ki-67 overexpression, and c-KIT mutations were associated with progression-free survival. Incomplete resection and mitotic activity also provide information about overall survival. In conclusion, complete clinicopathological, immunohistochemical, and genetic descriptions are necessary to characterize this disease and optimize its clinical management.