Studies have shown that COX-2 is up-regulated in several epithelial carcinomas. In this study, we wish to elucidate if endometrial cyclooxygenase-2 (COX-2) expression in endometrial adenocarcinoma is increased relative to normal endometrium. Thirty-six deparaffinized tissue sections from patients with endometrial adenocarcinoma were analyzed by immunohistochemistry for the presence of COX-2. A control group consisted of 13 age-matched patients without malignancy, who underwent surgery for uterine prolapse. Statistical analysis was performed using the Kruskal-Wallis test; differences between groups were evaluated using the Fisher's Exact Test. We found that COX-2 expression was markedly increased in 13 of 36 patients (36.1%) with endometrial adenocarcinoma: in contrast only one of 13 (7.7%) control patients demonstrated increased COX-2 expression (p < or = 0.05). Eight of the 13 COX-2 positive patients in the study had well differentiated adenocarcinoma; the remaining five COX-2 positive patients had moderately and poorly differentiated adenocarcinoma (4 and 1, respectively). In conclusion, COX-2 expression in the endometrium is associated with endometrial adenocarcinoma, especially of the well differentiated type. This may provide an avenue for chemoprevention of endometrial adenocarcinoma. In addition, with new selective inhibitory drugs being developed, inhibition of COX-2 may play an adjunctive role approach to standard therapy, especially for well-differentiated endometrial carcinoma. Further studies are required to investigate the role of COX-2 expression in carcinogenesis.