Objective  To determine the presence of p53 serum antibodies in patients with clinically well‐defined urological cancer using a new enzyme‐linked immunosorbent assay (ELISA). Patients and methods  The study included 73 patients with prostatic cancer, 72 with transitional cell carcinoma of the urinary tract, 37 with renal cell cancer and 16 controls with a benign disease, all of whom were tested using the ELISA for p53 autoantibodies. The specific reaction of the ELISA (positive p53 antibody titre) was confirmed by Western Blot analysis. Results  Thirteen patients with cancer and one control patient (7.6% overall) were positive for p53 autoantibodies. The sensitivity of the test was low, whereas the specificity was remarkably high. Surprisingly, 9 of the 13 p53‐positive patients died within a median of 3.7 months (range 2–6) and the one positive control patient died of undetected lung cancer. There was no significant correlation of p53 antibody positivity with clinical stage or tumour‐specific differences. Conclusions  The expression of p53 autoantibody seems to be a very late but significant event in urological tumour development, with the worst outcome (tumour‐specific death) within a few weeks of developing positivity. In histopathologically heterogeneous tumour entities, p53 autoantibodies might be independent prognostic factors in patients with urological cancers.