The gene responsible for MEN-2, the ret proto-ocogene, has elucidated mechanisms of endocrine tumorigenesis. Activating mutations of this transmembrane tyrosine kinase receptor represent the first known example of an inherited oncogene. This knowledge has altered our approach to affected patients by allowing in utero screening and prophylactic thyroidectomy rather than provocative testing and morphologic analysis of C cell hyperplasia--will it result in eradication of medullary carcinoma of thyroid? The lessons from Chernobyl taught us how radiation can induce chromosomal rearrangements that involve the same gene. This has led to a better understanding of papillary thyroid carcinoma and provides a novel immunohistochemical marker that widens our diagnostic armamentarium.