Various forms of modern therapy of urinary bladder cancer are associated with characteristic changes. Surgical therapy related morphology alterations usually do not present significant differential diagnostic problems. Postoperative spindle cell nodule may resemble a spindle cell sarcoma, but the fact that it arises within 120 days following surgery makes the diagnostic interpretation less cumbersome. Changes induced by BCG include epithelial denudation of the bladder, small superficial granulomas and chronic inflammation. Other forms of immunotherapy are associated with formation of lymphatic follicles or diffuse lymphocytic infiltrates. Radiation induced changes may appear many years after therapy and include atypia, bizarre appearance and multinucleation of urothelial cells. In the late phase, stroma is particularly affected. It is important not to misdiagnose radiation induced changes for CIS or invasive nested carcinoma. Chemotherapy-induced atypia may be recognized cytologically and histologically by the characteristic changes of the nuclear/cytoplasmic ratio, multiple nuclei, nuclear vacuolization, and architectural disturbances in the bladder epithelium. Photodynamic therapy induces sharply demarcated necrosis in the short post-therapy course. Laser treatment destroys the tumor, and may induce atypia in adjacent endothelial cells. Gene therapy-related changes have not been well defined yet.