SMAD4 is a tumor suppressor gene encoding an intracellular mediator in the transforming growth factor β (TGF β) signal transduction pathway. SMAD4 mutations have been reported in up to 2% of urothelial carcinomas. The predictive and prognostic significance of SMAD4 mutations in urothelial carcinoma needs further elucidation. Results should be interpreted in conjunction with other laboratory and clinical findings.