Multiple endocrine neoplasia type 2 (MEN 2) is characterized by the presence of medullary thyroid cancer (MTC) and other benign pathologies. RET mutations are responsible of this disease and their screening is a very sensitive tool for the identification of gene carriers (GC). Aim of this study was to verify the relevance of the basal and pentagastrin (Pg) stimulated serum calcitonin (CT) in the decision to perform TT in GC. We reviewed data of 65 GC found among 807 subjects screened for RET mutations. Twenty GC were negative for both basal and stimulated CT and, following our indications, did not undergo surgery. Thirty-five patients underwent TT on the basis of detectable levels of basal and/or stimulated CT. Twenty-one cases had an undetectable basal serum CT while 14 cases had detectable basal CT (15?922 pg/ml). All cases with undetectable basal CT levels or if detectable less than 60 pg/ml showed only C cell-hyperplasia ( n =5) or microfoci of MTC without node metastases ( n =22). Only cases with basal CT higher than 60 pg/ml ( n =8) showed either small MTC associated with node metastases ( n =4) or bigger MTC with or without node metastases ( n =4). Six GC with positive Pg-test refused TT and 4 are under evaluation. The correlation with the RET mutation showed that all GC with a cysteine mutation had a detectable basal and/or a Pg stimulated CT while no cysteine mutations were found among the 20 GC with undetectable values of basal or