BACKGROUND The purpose of our study was to examine the frequency of p53 mutation and bcl-2 expression in transitional cell carcinoma of the urinary bladder and their clinicopathologic correlates. METHODS A total of 137 patients who underwent transurethral resection for primary transitional cell bladder carcinomas were enrolled. The paraffin-embedded tissue blocks were recut and stained by monoclonal anti-p53 (DO7) and anti-bcl-2 (124) antibodies. The bcl-2 and p53 immunoreactivity was correlated to tumor grade and pathological stage. RESULTS p53 mutation was identified in 102 patients (78.5%). The mutation was most common in grade 3 tumors (95%) as compared to grade 2 (74%) and grade 1 (80%) tumors, but the difference was not statistically significant (p = 0.289). Stage pT2 tumors had higher incidence of p53 mutation (97%) as compared to pTa-1 tumors (71%, p = 0.0003). Only 17 tumors (13%) expressed bcl-2; the grade 3 tumors had significantly higher incidence of bcl-2 expression (p = 0.04). The bcl-2 expression was not related to pathological stage (p = 0.083). There was no interrelation between p53 mutation and bcl-2 expression (p = 0.97). Grade 3 tumors correlated well with invasive disease (p < 0.00001). When grade 2 tumors were evaluated separately, p53 mutation was positively correlated with disease invasion (p = 0.001). CONCLUSIONS Grade 3 tumor was the most important variable associated with tumor invasion in transitional cell carcinoma of the urinary bladder. p53 mutation was positively correlated with invasive disease. Grade 2 tumors with p53 mutation had greater probability of disease invasion. Expression of bcl-2 positively correlated with tumor grade but not pathological stage.