PURPOSE: Gastrointestinal stromal tumors (GISTs) are the most common form of mesenchymal tumor of the gastrointestinal tract. Recently, tyrosine kinase inhibitors have improved the treatment of GISTs, and their diagnosis facilitated by immunohistochemical markers. The aim of this paper was to study the clinicopathological features of GISTs of the stomach and determine the accuracy of a new grading system and the prognostic factors. METHODS: Patients with mesenchymal tumors of the stomach, operated on between 1982 and 2004, were identified using medical and pathological files. Immunohistochemical staining for KIT (CD117), CD34, smooth muscle actin (SMA), desmin and s-100 protein were performed, and the diagnoses reviewed. Cases were classified into either the very low, low, intermediate or high risk groups according to National Institutes of Health (NIH) consensus symposium. RESULTS: 78 mesenchymal tumors were reanalyzed, and with the supportive use of immunohistochemical markers, 71 (91%) of the gastrointestinal mesenchymal tumors were shown to be GISTs. The tumors often coexpressed KIT and CD34 (90%) and were variably positive for SMA (18%), s-100 protein (11%) and desmin (23%). With a median follow-up of 73.9 months (range 1~228 months), a recurrence occurred in 10 (14%) patients. Analyses demonstrated that the mitotic index (P<0.001) and tumor size (P<0.001) were significant prognostic factors for survival. The new grading system showed a significant difference between the risk groups and the survival rates (P<0.001). CONCLUSION: Immunohistochemical staining is needed to distinguish GISTs from other mesenchymal tumors. The tumor size and mitotic count are significant prognostic factors for GISTs. The new grading system (2001 NIH) for classifying the 4 risk groups of GISTs, according to the tumor size and the mitotic count, is useful in the evaluation of the tumor behavior.