There is a suggested pathogenetic role of cyclooxygenase-2 (COX-2) in endometriosis via angiogenesis and proproliferative mechanisms. The aim of the study was to investigate the immunohistochemical COX-2 expression in different anatomical sites of endometriosis and its correlation to proliferative activity and periendometriotic vascularization. Sixty endometrioses from different sites (ovarian, uterine, and peritoneal) were evaluated immunohistochemically for COX-2 expression. Cyclooxygenase-2 staining of 75% or more of the cells was defined as COX-2 overexpression and used as cutoff. Proliferative activity was determined by performing Ki-67-labeling index. Periendometriotic vascularization was evaluated by determining microvessel density surrounding the endometriotic focus using CD-34-immunostaining. Cyclooxygenase-2 overexpression was significant more frequent in ovarian endometriosis, when compared with uterine and peritoneal localization (70.8% versus 41.7%; P = .027). There was no significant correlation between COX-2 overexpression and perifocal neovascularization (P = .49). Endometriotic lesions with COX-2 overexpression represented reduced proliferative activity (P = .055). Cyclooxygenase-2 is expressed in the majority of endometriosis, but differences exist within the frequency of overexpression at different anatomical sites of the endometriosis. Cyclooxygenase-2 inhibitors are of clinical interest as treatment options.