PURPOSE: Cyclooxygenase-2 (Cox-2) is an inducible enzyme that converts arachidonic acid to prostaglandins. Aberrant expression of Cox-2 and prostaglandins has been observed in many cancers, including colon and breast cancers, and 40% of human breast cancers show overexpression of Cox-2. The aim of this study was to analyze the role of Cox-2 expression in breast cancers. METHODS: The expression of Cox-2 and HER2 was examined in 56 breast tissue samples including microscopically normal epithelium and invasive ductal carcinomas (IDC) using immunohistochemical (IHC) methods. Frozen breast cancers and adjacent non-cancerous tissue (ANCT) pairs (n=30) were analyzed for Cox-2 and HER2 mRNA expression by RT-PCR. The results were compared with the prognostic parameters of breast cancer including tumor grade, growth pattern, lymph node metastasis, estrogen receptor status and Ki-67 labeling index. RESULTS: Cytoplasmic Cox-2 expression was detected in 39 of 56 (69.6%) IDC and the Cox-2 expression in IDC was closely associated with HER2 expression (P=0.023). However, the expression of Cox-2 was not associated with other prognostic parameters of breast cancer (P>0.05). The Cox-2 mRNA showed high expression levels in IDC (25/30, 83.3%) as well as ANCT (22/25, 88%). CONCLUSION: The association between the expression of Cox-2 and HER2 suggests that Her2/neu gene induces the Cox-2 expression in breast cancer and overexpression of Cox-2 is involved in breast cancer development. Though the cells of ANCT are normal in morphology, their molecular alteration (overexpression of Cox-2) suggests that these cells have transformed already.