We examined Bcl-2, Bax and p53 expression in transitional epithelium, benign lesions derived from transitional epithelium (Brunn's nests and inverted papillomas) and transitional cell cancer (TCC) of the upper urinary tract and urinary bladder using immunostaining of cryostat sections. We also performed Western blot analysis of normal urothelium and TCCs for Bcl-2 and p53. Immunohistochemical staining showed that Bcl-2 was expressed only on basal layer cells, whereas Bax expression was restricted to superficial layers in normal transitional epithelium. Benign lesions of the urinary bladder (Brunn's nests and inverted papillomas) showed strong immunoreactivity to Bcl-2. Taken together, 16 (17%) TCCs were positive for Bcl-2, 62 (64.6%) TCCs were positive for Bax and 28 (29%) TCCs were positive for p53. The expression of Bcl-2 on TCC had a statistical correlation with tumor stage, histopathologic grade and p53 protein accumulation. The results suggest that although Bcl-2 overexpression is detected in normal urothelium and benign lesions of the urinary bladder, it might also contribute to the high grade tumor malignancy of TCC.