We evaluated tissues for the overexpression of p53 protein in 35 malignant mesotheliomas and 20 reactive pleural hyperplasias, obtained from open biopsies or pleurectomies. Of the 35 neoplasms investigated, 30 (85.7%) displayed positive nuclear staining for p53. No staining was seen in any specimens of hyperplasia. We found no significant statistical difference in p53 expression when we compared p53 overexpression in the different histological subtypes of mesotheliomas. Moreover, p53 overexpression did not correlate in a statistical manner with survival. We conclude that p53 overexpression is a frequent feature of pleural mesothelioma and is useful for routine differentiating between malignant and non-neoplastic mesothelial alterations. The reason for p53 overexpression in mesothelioma, however, remains to be determined.