RET is greatly involved in all aspects of MTC management: (1) discovery of a RET pathogenic germline variant leads to the diagnosis of MEN2, (2) presence of a RET pathogenic variant, at both the germline and somatic levels, predicts tumour aggressiveness and, lastly, (3) presence of a RET pathogenic variant enables specific therapy such as tyrosine kinase inhibitor to be employed. The gene discussed is RET; the disease is neoplasm.