AIM: To investigate the role of vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 and 2 in the growth and differentiation of gastrointestinal stromal tumors (GISTs).METHODS: Thirty-three GISTs, 15 leiomyomas and 6schwannomas were examined by immunohistochemistry in this study.RESULTS: VEGF protein was expressed in the cytoplasm of tumor cells, and VEGFR-1 and 2 were expressed both in the cytoplasm and on the membrane of all tumors.Immunohistochemical staining revealed that 26 GISTs(78.8%), 9 leiomyomas (60.0%) and 3 schwannomas(50.0%) were positive for VEGF; 24 GISTs (72.7%), 12leiomyomas (80.0%) and 4 schwannomas (66.7%) were positive for VEGFR-1; 30 GISTs (90.9%), 5 leiomyomas (33.3%) and 4 schwannomas (66.7%) were positive for VEGFR-2. VEGFR-2 expression was statistically different between GISTs and leiomyomas (P ＜ 0.0001). However,there was no correlation between the expression of VEGF pathway componenets and the clinical risk categories.CONCLUSION: Our results suggest that the VEGF pathway may play an important role in the differentiation of GISTs, leiomyomas and schwannomas.