This study immunohistochemically demonstrates p53 oncoprotein overexpression on routinely processed choroidal melanomas by means of four different anti-p53 antibodies after high-temperature antigen retrieval. The results were correlated both with morphologic and clinical parameters. Routinely formalin-fixed and paraffin-embedded tumor tissues from 43 choroidal melanomas were immunohistochemically investigated with four different anti-p53 antibodies directed against four different epitopes (CM-1, DO-7, PAb1801, PAb240) after wet autoclave antigen retrieval. The application of this technique is of outstanding importance for the demonstration of p53 protein on routinely processed tissues. Five patients (11.6%) of 43 showed more than 10% p53-positive tumor cell nuclei, which was regarded as p53 overexpression; these five patients underwent preoperative telecobalt or ruthenium irradiation. An additional 18 patients (41.9%) showed a few positively stained nuclei with at least one of the antibodies applied. p53 expression was more often found in epithelioid cell tumors; there was no statistical correlation between p53 overexpression and the clinical outcome. Our results suggest that p53 oncoprotein overexpression in choroidal melanomas indicates a late event in the progression rather than a crucial step in the development of these tumors. This conclusion is supported by the finding that all tumors with immunohistochemical p53 overexpression underwent preoperative irradiation, which might have caused p53 alteration(s) and thus enabled its immunohistochemical demonstration.