The aim of the current study was to compare the role of p53 and human papillomavirus (HPV) in schistosomiasis-related and schistosomiasis-unrelated carcinoma of the urinary bladder. To achieve this aim, we investigated 114 bladder carcinomas for p53 oncoprotein expression by immunohistochemistry and for human papillomavirus by in situ hybridization technique. The results revealed that 64 tumors (56.1%) were schistosomiasis-associated. Sixty seven (58.8%) were transitional cell carcinomas and 32 (28%) were squamous cell carcinomas. The remaining 15 tumors (13.2%) included adenocarcinomas and sarcomatoid carcinomas. In both schistosomiasis-associated and non-associated carcinomas, p53 oncoprotein expression was significantly higher in poorly differentiated tumors. However, it was significantly higher in locally more invasive tumors in the schistosomal carcinomas only. HPV types 16/18 could be detected in 1 of the 114 bladder carcinomas (0.95%), which was schistosomiasis-related squamous cell carcinoma in situ. These results suggest that p53 immunohistochemistry can be a prognostic factor in both schistosomal and nonschistosomal bladder cancer. More importantly, HPV does not seem to play a role in the pathogenesis of either type of bladder cancer in our country.