We have studied the expression of vascular endothelial growth factor (VEGF) in esophageal cancer using immunohistochemistry. A total of 101 specimens of esophageal cancer tissue were fixed by formalin, embedded in paraffin wax, and examined in 3μm sections by avidin-biotin peroxidase complex method. VEGF was noted in the cytoplasm of normal esophageal glandular cells, monocyte-macrophages, squamous carcinoma cells and of the vascular endothelial cells themselves. VEGF expression by monocyte-macrophages was observed in all cases, in contrast the incidence of VEGF expression in the tumor cells was relatively low at 26.7% of all specimens. However, in the cases where the tumor cells were positive for VEGF, it was discovered that the main source of the VEGF production was the tumor cells themselves. In the cases with proper mucosal invasion the incidence of VEGF expression by the tumor cells was quite low at 7.6%. However, when the tumor invaded the submucosal layer the expression increased to 33.3%. There was also a significant correlation in those with the submucosal invasion between the expression of VEGF in the tumor cells and the density of microvessels at the tumor invasive edge. These results suggest that VEGF may play an important role in tumor progression and in the angiogenesis via auto-crine and para-crine mechanisms in esophageal cancer.