BACKGROUND While current pathological and clinical parameters provide important prognostic information, they still have a limited ability to predict the true malignant potential of most bladder tumors. Therefore, the present study was carried out to investigate the levels of anti-apoptotic proteins such as p53 and Bcl-2, and of apoptosis itself as reflected by the increase in sub-G1 peak staining, in the blood and urine of bladder cancer patients, and to thus determine the usefulness of these parameters as tools for early and accurate prediction of tumor growth and development of metastases, in order to assess treatment benefit potential. METHODS A total of 80 bladder cancer patients and 50 healthy controls without malignancies were enrolled in this study. The levels of p53, Bcl-2 and apoptosis (sub-G1 peak) were evaluated by flow cytometry in the urine and blood of patients and controls. RESULTS Levels of p53, Bcl-2 and apoptosis were significantly higher in the urine sediment than in the blood. Moreover, p53 levels in the blood and urine of bladder cancer patients were significantly higher than in controls, and were significantly increased during the development of tumor grades and in association with positive parameters of urine analysis. In contrast, Bcl-2 and apoptosis levels in the blood and urine of bladder cancer patients were significantly lower than in samples from controls, and were significantly decreased during the development of tumor grades and in association with positive parameters of urine analysis. Apoptosis levels were positively correlated with Bcl-2 levels but negatively correlated with p53 levels. CONCLUSIONS These findings suggest that quantitative analysis of p53, Bcl-2 and apoptosis, especially in the urine sediment, may be a useful tool in the diagnosis of bladder cancer.