Undifferentiated small cell carcinoma of the bladder is a rare tumor with pathologic features similar to those of oat cell carcinoma of the lung. This neuroendocrine neoplasm of the bladder has a highly malignant biological behavior; most patients present with either locally advanced or distant metastatic disease and die despite aggressive therapy. Here the histologic, immunocytochemical, and ultrastructural features of small cell carcinoma of the bladder are reviewed in detail. In addition, two patients with advanced small cell carcinoma of the bladder who were treated successfully with radical cystoprostatectomy and adjuvant methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy (M-VAC) are presented. Both men had regional lymph node involvement and are disease free at follow-up of 1 year and 2.5 years, respectively. This is the first report of combined surgical and M-VAC chemotherapy in the treatment of undifferentiated small cell carcinoma of the bladder.