Mutations in the p53 gene are the most common genetic alterations found in human malignancies. In this study, a search was done for mutations in the conserved regions of the p53 gene in malignant mesotheliomas. Thirteen malignant mesotheliomas collected over the preceding 12 yr and maintained in paraffin blocks were examined by polymerase chain reaction (PCR) followed by both single-strand conformation polymorphism (SSCP) and denaturing gradient-gel electrophoresis (DGGE). Direct sequence analysis was performed in cases suspected for mutations. No mutations in exons 5 to 8 of the p53 gene were detected. Our results suggest that malignant transformation of human mesothelioma cells does not require inactivation of p53 by point mutations in the conserved regions of the gene.