The clinical utility of immunohistochemistry in the diagnosis of tumors of the urinary bladder is well established. With recent advances in molecular biology and novel technologies, several biomarkers have emerged as important adjuncts in the diagnosis of lesions of the bladder. When used in conjunction with careful histologic examination, immunohistochemistry can be a valuable aid in classifying adenocarcinoma presenting in the bladder and mesenchymal lesions of the bladder and in establishing the urothelial origin of a metastatic tumor. In addition, a number of biomarkers may prove to be important indicators of prognosis or response to chemotherapy.