Nasopharyngeal carcinoma (NPC) is the third most common cancer in the southern provinces of China, but a rare cancer in other parts of the world. Epidemiological studies suggested a multifactorial etiology of NPC involving infection of Epstein Barr virus (EBV), genetic predisposition, environmental factors, such as consumption of salted fish, and other unknown factors. p53 mutation is a common event in many forms of human cancers but its possible involvement in the pathogenesis of NPC has not been examined. The presence of p53 mutation in NPC is studied by the sensitive PCR-SSCP analysis and direct DNA sequencing method. The frequent sites of p53 mutation (exons 4 to 8) reported in other human tumors were studied. Thirty-eight biopsied tumors of NPC and 4 NPC cell lines were examined for the presence of p53 mutation. No mutation of p53 resulting in change in amino acid sequence of the encoded p53 protein was identified in any of the biopsies tumors. RFLP studies of the biopsied materials of NPC also revealed no loss of heterozygosity at chromosome region 17p13 in 15 out of 15 informative cases, which further supports the conclusion that p53 mutation is an infrequent event in NPC. Apparently, p53 mutation has no significant role in the pathogenesis of this special group of human cancers. However, p53 mutation is frequently observed in cell lines derived from the primary NPC tumors. All the three NPC cell lines examined carry a missense p53 mutation, suggesting that mutation of the p53 gene may confer growth advantage to the tumor cells to become established in culture.