In order to investigate the implications of cyclooxygenase-2 (COX-2) expression in combination with Ki-67 on breast cancer outcomes, the COX-2 and Ki-67 expression levels and other clinicopathologic parameters were investigated in 861 breast cancers. Clinicopathological parameters and survival were investigated in association with the expression levels of both COX-2 and Ki-67 using univariate and multivariate analyses. COX-2 expression was positive in 493 (57.3%) of invasive tumors. COX-2 was associated with favorable markers, but was not related to survival outcome by itself. However, COX-2 in proliferative tumors [COX-2(+)/Ki-67(+)] were significantly associated with unfavorable factors and the worst survival, but COX-2 in non-proliferative tumors [COX-2(+)/Ki-67(-)] showed significantly favorable parameters and better outcomes. COX-2(-)/Ki-67(any) showed intermediate prognosis. The statistical significance was maintained in stage-matched and multivariate analyses. The results of present study suggest that COX-2 expression is a common event in breast cancers and may play in a different ways by the proliferation status of the tumor cells. Further studies should be carried out to verify the role of COX-2 by proliferative conditions of breast tumor cells.