The human RET (REarranged during transfection) gene maps on chromosome 10q11.2 and codes for a single pass transmembrane protein.The intracellular portion features a typical tyrosine kinase domain.RET is expressed primarily in peripheral enteric, sympathetic and sensory neurons, and in central motor, dopaminergic and noradrenergic neurons. Activating germ line point mutations in RET cause three related dominantly- inherited cancer syndromes:multiple endocrine neoplasia type 2A (MEN2A), 2B (MEN2B) and familial medullary thyroid carcinoma (FMTC). MEN2-associated RET mutations have a gain of function effect, i.e., they promote activation of the kinase and oncogenic conversion.The first evidence of RTE involvement in himan cancer was obtained in thyroid papillary carcinomas. Chromosomal inversions or translocations of 10q11.2 occur in 2.5% to 40% of papillary thyroid carcinomas (PTC). RET is a suitable target for the design of novel therapeutic approaches for human cancer.