Overexpression of the TP53 gene protein detected by immunohistochemistry appears to identify those patients with superficial bladder cancer at risk of the development of muscle invasive or metastatic disease. However, the role of p53 overexpression in patients with advanced or metastatic bladder cancer is not yet well established. In the present study, 44 specimens from 44 patients with advanced stage bladder tumours (T2-T4) undergoing radical cystectomy were investigated for different biological and clinical characteristics as possible prognostic factors: sex, age, depth of tumour infiltration, T-stage, histological grade, lymph node status, application of adjuvant systemic chemotherapy (MVAC), proliferative activity (staining for proliferating cell nuclear antigen (PCNA) by monoclonal antibody (PC10) as well as overexpression of the p53 oncoprotein (monoclonal antibody pAb 1801)). After a median follow-up of 22 months, 16 of the 23 patients (70%) with more than 40% of tumour cells stained positively for p53 (Group B) died from tumour progression compared with 7 of the 21 patients (33%) with less than 40% of tumour cells positive for p53. During univariate analysis, p53 overexpression (P = 0.008), staining for PCNA (> or = 80% of cells positive) (P = 0.01) and tumour stage (P = 0.01) were significant prognostic factors for survival, among which p53 overexpression (P = 0.023) as well as T-stage (P = 0.012) remained independent significant predictors during multivariate analysis. Prospective studies are needed to confirm the independent prognostic potential of p53 overexpression in patients with advanced bladder cancer. The availability of more refined prognostic factors should assist decision making regarding the value of more aggressive treatment options, such as adjuvant or neoadjuvant chemotherapy, for prognostically defined subgroups of patients.