Numerous biologic processes and such diseases as cancer depend on activation of tyrosine kinase receptors. The RET tyrosine kinase receptor was discovered two decades ago as a transforming gene and was subsequently implicated in the formation of papillary and medullary thyroid carcinoma. This article examines the data about the mechanism of activation of downstream signal transduction pathways by RET oncoproteins. Collectively, these findings have advanced the understanding of the processes underlying thyroid carcinoma formation.