The biologic behavior of gastrointestinal stromal tumors is difficult to predict, and they can be best studied in a site-specific fashion. The aims of this study are to analyze the clinicopathologic parameters and assess the prognostic value of p53 (DO-7) and Ki-67 (MIB-1) immunoreactivities in small intestinal stromal tumors (SIST). The histopathologic features of 31 SIST were assessed and categorized into two groups as follows. Group A (clinically aggressive) in which death due to tumor, metastasis, recurrence or relapsed melena were seen (n = 15) and group B (clinically benign; n = 16). For both groups, the period of follow-up was 30-144 months. p53 overexpression was observed in four tumors (31%) in group A, and in none in group B. For groups A and B, the mean Ki-67 index was 16.8 +/- 12.5 and 8.4 +/- 12.6, respectively. Statistical analysis revealed that the significant predictors of malignancy were high cellularity (odds ratio (OR) = 999; 95% confidence interval (CI) = 0-999); p53 overexpression (OR = 999; CI = 0-999); size of tumor > or = 5 cm (OR = 18.0; CI = 1.9-171.9); > or = 5 mitoses/50 high-power fields (HPF) (OR = 17.1; CI = 1.8-165.9); pleomorphism (OR = 17.1; CI = 1.8-165.9); and necrosis (OR = 11.9; CI = 2.2-65.1; P < 0.05). High Ki-67 index (> or = 8.4) had a marginal impact on risk (OR = 4.1; CI = 0.8-20.2; P = 0.08). In conclusion, high cellularity, p53 overexpression, size of tumor > or = 5 cm, > or = 5 mitoses/50 HPF, pleomorphism and necrosis are important parameters for the prediction of malignancy in SIST.