RET/PTC oncogene expression is restricted to papillary thyroid carcinomas (PTC). At least three forms of this oncogene have been described. These are generated by the rearrangement of the 5'-terminal region of different expressed genes with the tyrosine-kinase (TK) domain of the ret proto-oncogene. Several studies showing the correlation between the expression of this oncogene, clinical outcome, and histological subtypes have been published. Thirty-five paraffin-embedded PTC samples from patients without a history of radiation exposure were studied. Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to determine a possible correlation between RET activation, clinical outcome, and tumor subtype. Almost half of the studied cases presented with tumoral extension or metastases. Ret gene transcripts and protein were found in all PTC variants as well as in their corresponding metastases. In contrast, none of the follicular adenomas, goiters, or normal follicular cells from the thyroid gland showed evidence of ret activation. We observed a high frequency of ret expression in PTCs, suggesting that ret activation is a common event in nonradiation-related PTC from Mexican patients.