In order to increase the sensitivity to immunostaining in formalinfixed, paraffin-embedded tissues, we developed an immunohistochemical method by microwave heating of tissue sections instead of trypsin digestion. The results of this study showed that there was no positive P53 protein reaction in normal and hyperplastic mucousa of human mouth, whereas 90% (27/30) of cases with dysplasia, 61% (30/49) of oral squamous cell carcinomas and 86% (13/15) of regional metastatic lymph nodes were positive. And all positive reactions were localized in nuclei. Comparison of these positive results of p53 gene mutation detected by silver staining method with the results by polymerase chain reaction-single strand conformation polymorphism analysis did not reveal matched results, especially during the precancerous period. The authors analysed the causes of difference not only by methodology, but also by cell groups which had different genetic changes in tissues of precancerous lesions.