The biological behavior of gastrointestinal stromal tumors (GISTs) are highly variable. To investigate the biological behavior of GIST, we collected 83 cases of gastric and 62 cases of small intestinal GIST from the Department of Pathology of the Chinese PLA General Hospital. The parameters include age, primary tumor location, tumor diameter, mitotic index, tumor necrosis, risk assessment, clinical stage and the c-kit exon 11 mutation. All these were analyzed in 105 cases along with the follow-up data and tested by log rank and COX hazard proportional model. We find that the average age of gastric GIST was 55.4 years. Of the 62 cases that were followed up, 17 cases had metastasis or recurrence and the 5-year survival rate was (66.51 ± 17.06)%. For the small intestinal GIST, the average age was 50.6 years and 43 cases were followed up. Of these, 22 cases had metastasis or recurrence and the 5-year survival rate was (61.76 ± 18.30)%. Small intestinal GIST was more frequently associated with metastasis and tumor relapse than gastric GIST (?2 = 6.131, P = 0.013). For gastric GIST, patients younger than 50 years (P = 0.046), the advanced clinical stage (P = 0.0001), the large tumor diameter (P = 0.0001), a high mitotic index (P = 0.0001), necrosis (P = 0.0001) and a high risk grade (P = 0.004) were all correlated with a lower survival rate. The COX hazard proportional model revealed that advanced clinical stage (P = 0.001), large tumor size (P = 0.001), a high mitotic index (P = 0.002) and the high risk grade (P = 0.018) indicated a poorer prognosis in gastric GIST. For small intestinal GIST, necrosis (P = 0.036) and advanced clinical stage (P = 0.010) were associated with lower survival rates and the clinical stage was shown to be an independent prognostic indicator. A total of 25 cases harbored mutations in c-kit exon 11. The frequency of c-kit mutation was 32% and 22.5% for gastric and small intestinal GIST, respectively. In gastric GIST, the mutated c-kit was predominant in patients older than 50 years of age. But in the small intestinal GIST, the mutated c-kit was predominant in the age group of 40–49 years. In conclusion, for gastric GIST, clinical stage, tumor size, mitotic index, and risk grade are the prognostic indicators. For small intestinal GIST, necrosis and clinical stage are the prognostic indicators. Small intestinal GIST are more aggressive than gastric GIST. The occurrence of c-kit mutation may correlate with the age of patients.