Objectives: To investigate the presence of ret and trk protooncogene rearrangements in thyroid tumors. Design and Methods: High-molecular-weight DNA was extracted from 36 thyroid tumors (1 multinodular goiter, 14 follicular adenomas, 16 papillary carcinomas, 1 lymph node metastasis of a papillary carcinoma, 1 follicular carcinoma, and 3 medullary carcinomas) and 22 adjacent tissues. Southern blot analysis was performed after digestion with EcoR1 or BamH1, using specific probes for ret and trk. Results: Only 2 ret rearrangements were found in 2 papillary carcinomas (overall frequency: 6%; papillary carcinoma frequency: 13%). All normal or tumor samples were negative for the presence of a trk rearrangement. Conclusions: The previous data from the literature are highly conflicting, ranging from 0 to 30% of activation. Our results could be, therefore, classified as medium between these extreme values. It seems, therefore, that genetic and/or geographical factors could play a role in ret and trk proto-oncogene activation.