Bladder tumors as the most common urologic malignancy present mostly as superficial transitional cell carcinoma. Many patients with superficial bladder cancer have a good prognosis, however, may develop recurrences or progress to muscle invasive or metastatic disease. It is therefore important to find new markers associated with the biological behaviour of an individual tumor for identifying patients at risk for disease progression. Previous reports on the prognostic significance of p53 alterations in bladder tumors revealed conflicting results. The aim of our study was to evaluate p53 mutation analysis as an effective concept for the characterization of subsets of superficial bladder tumors differing in biological aggressiveness. Screening 66 amplified DNA from micro-dissected tumor cells by direct genomic sequencing p53 alterations were detected in 12%. We found no association between p53 status and tumor stage but a tendency to a higher mutation rate in more malignant tumors (G2 and G3) compared to G1 tumors and a higher recurrence rate in patients with a p53 mutation in the primary tumor after 24 months follow-up. We conclude a general low incidence of p53 mutations in superficial bladder cancer. Detectable p53 damage might be related to a more aggressive phenotype and a higher recurrence risk. Our results are discussed in the context of other studies reviewed from 1995-2000.