The expression of immunohistochemical markers that have been used in diagnosis and/or prognostication of urothelial tumors in humans (uroplakin III [UPIII], cytokeratin 7 [CK7], cyclooxygenase-2 [COX-2], and activated caspase 3) was evaluated in a series of 99 canine proliferative urothelial lesions of the urinary bladder and compared to the lesion classification and grade as defined by the World Health Organization / International Society of Urologic Pathology consensus system. There were significant associations between tumor classification and overall UPIII pattern (P = 1.49 x 10^–18), loss of UPIII (P = 1.27 x 10^–4), overall CK7 pattern (P = 4.34 x 10^–18), and COX-2 pattern (P = 8.12 x 10^–25). In addition, there were significant associations between depth of neoplastic cell infiltration into the urinary bladder wall and overall UPIII pattern (P = 1.54 x 10^–14), loss of UPIII (P = 2.07 x 10^–4), overall CK7 pattern (P = 1.17 x 10^–13), loss of CK7 expression (P = .0485), and COX-2 pattern (P = 8.23 x 10^–21). There were no significant associations between tumor classification or infiltration and caspase 3 expression pattern.