Cyclooxygenase (COX), which catalyzes the synthesis of prostaglandins from arachidonic acid, has two isoforms; COX-1 and COX-2. A large body of evidence exists to suggest that COX-2 is important in gastrointestinal cancer. In order to determine whether COX-2 is expressed in transitional cell carcinoma (TCC) of the human bladder as well as in gastrointestinal cancer, we investigated COX-2 expression in human TCC by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunohistochemical analysis, and we found that normal bladder epithelium did not express COX-2 and that COX-2 was markedly up-regulated in human bladder TCC. In nontumor tissues, COX-2 immunostaining signals were observed only in lymphoid follicles. Furthermore, the intensity and extent of COX-2 immunostaining in the bladder cancer tissues were scored and the relationship to tumor grade and stage was investigated. The levels of COX-2 expression were correlated with the tumor grade; from grades I to 3, there was a stepwise increase in the COX-2 immunostaining score. These findings suggested that an increase in COX-2 expression may be associated with bladder carcinogenesis as well as gastrointestinal carcinogenesis, and that it may be useful as a biomarker in bladder cancer.