OBJECTIVE The mitotic index and tumor size are currently the main prognostic indicators of gastrointestinal stromal tumors (GIST). The purpose of this study is to investigate the expression of different immunohistochemical markers and their relation to mortality and relapse, and especially concerning high-risk tumors. METHODS We did a retrospective study of 68 patients who underwent surgery from 1997 to 2007 with a diagnostic of gastrointestinal stromal tumor. RESULTS The median follow-up period was 29 months. Relapse and mortality rates were 35.3% (24 cases) and 41.2% (28 cases), respectively. The mitotic index was related to p53 and the cellular proliferation index -Ki67- (p = 0.006 and p = 0.003, respectively). Considering both high and intermediate-risk neoplasms, a significant relation to Ki67 was obtained (p = 0.008). Relapse was related to the mitotic index (p = 0.032) and Ki67 (p = 0.024). Concerning mortality, statistically significant results were obtained with necrosis variables (p = 0.02), mitotic index (p = 0.013), p53 (p = 0.024) and Ki67 (p = 0.033). CONCLUSIONS Ki67 could be considered a prognostic marker for both relapse and mortality. Concerning high risk GIST, the usefulness the p53 protein and Ki67 nuclear antigen markers was also evident concerning relapse and mortality.