Accumulation of the p53 protein has been found in several types of lymphomas. However, p53 gene mutations have been infrequently demonstrated in some specific types of lymphomas. In the present study, a correlation between p53 immunoreactivity and p53 gene mutations in a large panel of non-Hodgkin's lymphoma (NHL) cases is attempted. A panel of 202 cases of NHL was evaluated by immunohistochemical staining for p53 protein. All cases that were immunohistochemically positive for p53 protein were analyzed by the polymerase chain reaction (PCR) single strand conformation polymorphism (SSCP) method to identify mutations within the p53 gene. In order to confirm the mutation, sequencing of PCR-amplified p53 gene segments was performed. Overexpression of p53 protein was found in 59 of the 202 cases of NHL, but only four of these 59 cases showed a shift on SSCP analysis, and point mutations were detected in three of them by the subsequent sequencing. p53 immunoreactivity was generally greater in high-grade lymphoma. The results of this study suggest that immunohistochemical reactivity for p53 protein is not a reliable indicator of the presence of their structural alterations of p53 gene exons 4-9 in NHL.