The proto-oncogene ets-1 is a transcription factor known to control the expression of a number of genes involved in extracellular matrix remodeling. To elucidate the involvement of ets-1 in human thyroid carcinoma, we examined 68 cases of thyroid carcinoma and 38 cases of benign tumors by immunohistochemical means. ets-1 was not expressed in normal thyroid follicular cells. Among the 69 cases of thyroid carcinoma, 61 (89.7%) showed positive staining for the ets-1 protein. According to histologic classification, 47 (97.9%) of 48 papillary carcinomas, 7 (87.5%) of 8 follicular carcinomas, 3 (60.0%) of 5 medullary carcinomas, and 4 (50.0%) of 8 anaplastic carcinomas showed positive staining of ets-1. Among the benign tumors, staining was positive for ets-1 in 8 (40.0%) of 20 adenomas and 3 (16.7%) of adenomatous goiters. In situ hybridization also confirmed the expression of ets-1 mRNA in thyroid carcinoma. Expression of ets-1 mRNA was seen in three kinds of cultured human thyroid carcinoma cell lines and carcinoma tissue obtained at surgery by reverse transcription-polymerase chain reaction. These findings suggest that ets-1 is deeply involved in thyroid carcinogenesis.