Cyclooxygenase is the rate-limiting enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. The inducible form, cyclooxygenase-2, is known to be overexpressed in various human cancers including the colon, stomach, and urinary bladder. In this study, we evaluated the overexpression of cyclooxygenase-2 in 64 cases of breast cancer and correlated the results with clinicopathologic parameters. Immunohistochemical staining for cyclooxygenase-2 demonstrated positivity of the tumor cells in 46 of 64 cases (72%). Cyclooxygenase-2 overexpression was significantly correlated with larger tumor size and advanced clinical stage. Cyclooxygenase-2 overexpression tended to be more frequently observed in cases with presence of lymph node metastasis and in cases without expression of estrogen and progesterone; however, there was no significant correlation statistically. Nuclear and histologic grade were not well correlated with cyclooxygenase-2 overexpression. When ductal carcinoma in situ was considered separately, 32 of 42 cases (76%) were positive for cyclooxygenase-2. We conclude that cyclooxygenase-2 is up-regulated in a high proportion of breast cancers. The overexpression of cyclooxygenase-2 was associated with larger tumor size and advanced clinical stage, although lymph node status, estrogen and progesterone expression, and nuclear and histologic grade were not significantly correlated. Therefore, cyclooxygenase-2 overexpression may be a feature of the aggressive phenotype and may be useful as a prognostic indicator in breast cancer.