The activation of RET proto-oncogene through chromosomal translocation is reported as being unique to papillary thyroid carcinomas. However, the reported prevalence of RET/PTC activation in papillary carcinoma was variable, and the clinical relevance of RET/PTC rearrangements in papillary carcinomas is still controversial. To investigate the roles of RET rearrangement in the carcinogenesis of papillary thyroid carcinoma, we have studied RET activation and p53 overexpression in various thyroid lesions of the Japanese population by immunohistochemical technique. RET activation and p53 overexpression were studied in 40 papillary carcinomas, 6 poorly differentiated carcinomas, 4 undifferentiated carcinomas, 2 medullary carcinomas, 2 follicular carcinomas and 19 follicular adenomas. RET activation was observed in 12 out of 40 papillary carcinomas, while no immunoreactivity of RET was detected in other lesions. P53 overexpression was observed in only 1 of 40 papillary carcinomas, but in 2 poorly differentiated carcinomas and 4 undifferentiated carcinomas. The prevalence of RET/PTC activation in papillary carcinoma among the Japanese population was higher than in previous reports. Immunohistochemical technique is proved to be a useful tool to detect RFT/PTC activation in thyroid tumors. RET rearrangements are restricted to a well-differentiated papillary carcinoma, suggesting that RET/PTC positive papillary carcinomas do not progress to undifferentiated carcinoma.