PURPOSE: Recent studies have shown that cyclooxygenase (COX)-2 may be involved in tumor growth, invasion and apoptosis in various carcinomas. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity, and COX-2 promotes angiogenesis by modulating angiogenic factors, including VEGF. Endothelial growth factor receptor (EGFR) is considered as a factor of cell growth, maturation and cell death. The current study was designed to investigate the possible roles of COX-2 in colorectal tumor progression and angiogenesis. METHODS: Fifty colorectal adenomas and forty adenocarcinomas were investigated by using immunohistochemical staining for COX-2, VEGF and EGFR. The correlations of COX-2, VEGF and EGFR with the grade of dysplasia, the size of the adenoma, and various clinicopathologic factors were studied. RESULTS: The expressions of COX-2, VEGF and EGFR were each significantly correlated with carcinomatous transformation, and the expressions of COX-2 and VEGF were significantly correlated. COX-2 and EGFR showed correlations with adenomas rather than adenocarcinomas. However, no correlations of COX-2, VEGF and EGFR expression to other clinicopathologic factors, except tumor size in EGFR expression, were detected. CONCLUSION: These results suggest that COX-2 may play an important role in carcinogenesis through interaction with VEGF and EGFR in human colorectal cancer.