Four cases of radiation cystitis that caused diagnostic difficulty because of an epithelial proliferation with architectural complexity and reactive cytologic atypia are described. The patients, 2 male, 2 female, were from 43 to 77 years of age. Two presented with hematuria. Cystoscopy disclosed abnormalities in 3 patients. Microscopic examination showed irregularly shaped and arranged aggregates of epithelial cells in the upper and mid zones of the lamina propria. The cells, which typically showed at least mild, and sometimes severe, pleomorphism, were usually transitional, but squamous differentiation was seen focally in 3 cases. Ulceration of the overlying epithelium was present in all cases and was prominent and associated with conspicuous fibrin and hemorrhage in one of them. Edema of the lamina propria was present in 3 cases, whereas lamina propria fibrosis and chronic inflammation were present in all cases. The presence in all 4 cases of vascular ectasia and other changes characteristic of radiation injury, such as atypical fibroblasts, prompted investigation of the clinical history in 2 cases in which the pathologist was unaware that the patient had received radiation. Pseudocarcinomatous proliferations in the bladder caused by radiation injury have received limited attention in the literature. Our cases illustrate the potential diagnostic errors with which these lesions may be associated.