Small cell carcinoma of the urinary bladder is a rare and highly aggressive tumor. P53 expression has been shown to be associated with poor prognosis in a variety of tumors. This study was undertaken to investigate p53 expression in a large series of small cell carcinomas of the urinary bladder and to correlate the findings with clinicopathologic parameters and clinical outcome. Pathologic findings were reviewed and were correlated with clinical findings and follow-up information. Immunohistochemical staining for p53 was performed on paraffin-embedded tissue sections using the avidin-biotin-peroxidase method. Results were recorded as positive expression (> or =10% of cells with nuclear staining) or negative expression (<10% of cells with nuclear staining). The series included 40 males and 10 females. All 50 patients except one had advanced disease (T2 or above) at presentation. Pathologic stages were as follows: T1 in 1, T2 in 25, T3 in 21, and T4 in 3 patients. During a median follow-up of 12 months (range: 1 month to 122 months), 38 patients died of cancer. Two-year and 5-year cancer-specific survival rates were 45% and 16%, respectively. P53 overexpression was present in 27 out of 50 (54%) cases (7 with 10-25% staining, 4 with 25-50% staining, 11 with 50-75% staining and 5 with 75-100% staining); conversely, negative staining for p53 was observed in 23 out of 50 (46%) cases (19 with no staining and 4 with <10% staining). No correlation was demonstrated between the level of p53 expression and survival (p =0. 16). The 5-year cancer-specific survival was 16.6% for patients with tumors expressing p53 in greater than or equal to 10% of cells and was 14.7% for patients with tumors expressing p53 in less than 10% of tumor cells. There was no correlation between p53 expression and other clinicopathologic characteristics, including age (p =0.20), gender (p=0.84), history of smoking (p=0.25), pathologic Tstage (p=0.38), clinical stage (p=0.60), lymph node metastasis (p=0.17), and distant metastasis (p=0.88). Our data indicate that p53 is frequently expressed in small cell carcinoma of the urinary bladder. However, no correlation is found between p53 expression and clinicopathologic parameters, including long-term survival.