Abnormalities of the gene encoding the sequence-specific DNA-binding protein, nuclear phosphorprotein p53, are among the most common genetic alterations observed in human cancers. A mutation of this tumor suppressor gene has been reported with a low prevalence in differentiated thyroid carcinomas, while the prevalence was high in undifferentiated thyroid carcinomas. We used denaturing gradient gel electrophoresis (DGGE) to probe for mutations of p53 gene in order to determine its role in the genesis of malignant thyroid lymphoma. Involvement of 27 samples had been proven by histopathologic examination of specimen obtained by open biopsy of the thyroid gland or from cervical lymph nodes. DNA was extracted from tissues embedded in paraffin blocks and exons 5-8 of p53 gene were examined for the presence of mutations by DGGE following amplification by PCR using GC-clamped primers. To confirm accuracy of the method, samples with known p53 mutations were included in the study. No mutations were detected in any of the amplified exons of malignant thyroid lymphoma samples. These results suggest that p53 mutations are not present or are uncommon in Japanese patients with malignant thyroid lymphomas. The role of p53 in this form of carcinogenesis cannot be fully excluded since we have not examined the occurrence of mutations in regions upstream of exon 5.