PURPOSE: Although gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors and express CD117, the prediction of their malignant potential remains difficult. The aim of this study is to evaluate the prognostic accuracy of elevated Ki67 index and p53 overexpression in combination with classical prognostic factors (tumor size and mitotic index). METHODS: A retrospective study was conducted in 84 patients who had been re-evaluated for confirmation of diagnosis based on immunohistochemical analysis with CD117 expression, between Jan 1991 and Dec 2001. Cases were classified as very low, low, intermediate and high-risk groups according to 2001 NIH consensus symposium. Elevated Ki67 index was assigned to the lesion that displayed 10% or more of immunoreactive cells. And p53 expression was assigned to the area with 5% or more of eosinophilic nucleus. RESULTS: Elevated Ki67 was noted in 37 (44.0%) out of 84 cases. High-risk patients showed elevated Ki67 index more frequently (P<0.0001) and there was significant relation between elevated Ki67 and survival rate (P=0.0417). The p53 expression was noted in 32 (38.1%) out of 84 cases. The p53 expression was significantly higher in high-risk patients (P=0.0081) than low-risk patients. But, there was no significant relation between p53 expression and survival rate. As a result of multivariate analysis, tumor size (P=0.0059), mitotic index (P=0.0016) and elevated Ki67 index (P=0.0384) were proved as significant independent prognostic factors. CONCLUSION: According to the results of our retrospective study, p53 expression is related to disease progression but its value as a prognostic factor in GISTs is uncertain. It is suggested that tumor size, mitotic rate and elevated Ki67 index are the helpful prognostic factors in GISTs.