BACKGROUND: Carcinoma of urinary bladder is one of the most common malignancies worldwide and constitutes a major health problem. Multiple risk factors are associated with this tumor and its prognosis will depend on different clinicopathological parameters. Over expression of P53 protein and mutant Rb gene is associated with more aggressive clinical and histopathological features of the tumor such as advanced stage and higher grade. AIM: The immunohistochemical expression of Rb gene and P53 gene will be assessed through their protein products in transitional cell carcinoma (TCC) of the urinary bladder and then will be correlated with other well-known risk factors and prognostic parameters of bladder TCC, such as grading, tumor size, smoking, alcohol drinking, and family history. METHODS: Patients were recruited from the uro-surgical department/Surgical Subspecialties Teaching Hospital during the period from November 2020 through April 2021. In this study, patients enrolled were those suspected to have bladder carcinoma. The work up included a full history and clinical examination. Surgical samples were taken from the patients for histopathological evaluation; the study’s samples represented either endoscopic cup biopsy, transurethral resection of the tumor, or radical cystectomy. Sections obtained from these samples were stained with the conventional hematoxylin and eosin stain. Then, immunohistochemical staining for P53 and pRB was applied only for patients diagnosed with TCC. RESULTS: The differences between low-grade and high-grade tumors regarding pRb percentage score were statistically significant (p = 0.026), but were not significant regarding the intensity score (p = 0.094). There were significant correlations between tumor stage and both pRb intensity and percentage scores (p = 0.044 and 0.042, respectively). Differences between low-grade and high-grade tumors regarding p53 intensity score were significant (p = 0.022). The differences between low-grade and high-grade tumors regarding p53 percentage score were significant (p = 0.049). The differences between different tumor stages regarding p53 intensity score were significant (p = 0.018). The differences between different tumor stages regarding P53 percentage score were significant (p = 0.019). CONCLUSIONS: Tumor’s grade was found to be correlated with the tumor stage with no correlation with the age, gender, smoking, family history of TCC, history of urinary tract infection, bladder stones, nor the recurrence of the tumor. The pRb intensity and the percentage scores were correlated to each other and to tumor’s grade and stage, except for the pRb intensity which showed no correlation with the tumor’s grade. The P53 intensity and percentage scores were correlated to each other and also to tumor’s grade and stage, so that P53 is over-expressed in tumors with higher grade and stage.