To investigate the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in extra-hepatic cholangiocarcinoma and the relationship between their expression and clinicopathological parameters.COX-1 and COX-2 were detected in 56 extra-hepatic cholangiocarcinomas, including 31 matched tissues originating from non-tumorous bile ductal tissue adjacent to tumours and 6 normal bile ductal tissues, by immunohistochemistry strept avidin-biotin complex using isozyme selective antibodies.There was no difference in expression of COX-1 between carcinomas (96%, 54/56) and noncancerous specimens (94%, 29/31, P>0.05) or normal bile ductal tissues (100%, 6/6, P>0.05). The positive rate of COX-2 expression in extra-hepatic cholangiocarcinomas (86%, 48/56) was significantly higher than their matched tissues (39%, 12/31, P<0.01) and normal bile ductal tissues (0%, 0/6, P<0.01). Overexpression of COX-2 in extra-hepatic cholangiocarcinoma was related to the metastasis of lymph nodes, distant organs or tissues (P<0.05) as well as the degree of tumour differentiation (P<0.05).The overexpression of COX-2 plays a crucial role in the carcinogenesis and development of extra-hepatic cholangiocarcinoma, indicating that COX-2 may serve as a target for chemoprevention of extra-hepatic cholangiocarcinoma.