Squamous cell carcinoma is an uncommon histologic type in the urinary bladder. We searched our surgical pathology files and identified 16 cases of squamous cell carcinoma of the urinary bladder. The mean age of patients was 65.4 years (range, 41-77 years). All patients received transurethral resection of the bladder, which demonstrated pure squamous cell carcinomas. Seven patients had clinical evidence of tumor spreading out of the bladder (T4) and did not undergo radical cystectomy. The other 9 patients underwent cystectomy with pelvic lymph node dissection. The cystectomy specimens revealed tumors invading muscularis propria (T2) (n = 4) or perivesical soft tissue (T3) (n = 5). Two patients also had metastasis to lymph nodes. Immunohistochemical studies demonstrated that squamous cell carcinoma cells were positive for epidermal growth factor receptor (n = 16) and for p53 (n = 11). For the 9 patients who received cystectomy, 5 patients were alive at a mean of 92.8 months (range, 59-128 months) and 4 patients died of disease at a mean of 24.0 months (range, 6-58 months). For the 7 patients who did not receive cystectomy, 6 died at a mean of 5.7 months (range, 3-9 months), and no follow-up was available for the remaining patient. In conclusion, squamous cell carcinoma of the bladder frequently presents at an advanced stage and is associated with enhanced expression of EGFR and p53.