We report the case of a 78-year-old man with metastatic transitional-cell carcinoma with squamous differentiation that responded dramatically to the monoclonal antibody agent, bevacizumab. The tumor originated in the bulbar urethra, with histology of poorly differentiated urothelial carcinoma. Metastasis to a right inguinal lymph node was biopsy-confirmed as transitional-cell carcinoma with areas of keratinization. At last follow-up, he had received 24 months of bevacizumab treatment with minimal toxicity and a positive response. Mediators of angiogenesis have been implicated in the clinical progression of bladder cancer, although the role of angiogenesis inhibitors as treatment has not yet been defined. The striking benefit achieved in this heavily treated patient suggests that bevacizumab could have clinically useful antitumor activity in advanced urothelial carcinoma.