Background and Objectives: Preoperative diagnosis of sporadic medullary thyroid carcinoma (MTC) has mainly relied on fine needle aspiration cytology (FNAC). The present study aimed to compare the sensitivity of this technique with serum calcitonin (CT) measurement and to assess the therapeutic implications of an inadequate preoperative diagnosis. Methods: We reviewed the clinical records of 91 MTC patients treated and/or followed at our institution between January 1990 and December 2003. Results: After revision of clinical records, 77 individuals were considered eligible for the study. FNAC was performed in 67 patients (87%) with a sensitivity of 63%; serum CT was measured in 56 patients (73%) with a sensitivity of 98%. Both FNAC and serum CT were assessed in 51 patients (66%). FNAC detected only 74.5% of MTCs suspected by elevated serum CT. Among patients with a cytological diagnosis of MTC, total thyroidectomy (TT) was performed in 95% of patients. Among patients without a cytological diagnosis of MTC, TT was performed in 83% of patients in whom serum CT was evaluated prior to surgery whereas it was performed in only 46% of patients in whom CT evaluation was lacking. Conclusions: Despite the higher sensitivity of serum CT measurement, as compared with FNAC to diagnose MTC (98% vs. 63%), only 9% of patients might have escaped to surgery based on FNAC results. However, indication for surgery based on suspicious FNAC may not alert the surgeon for the need of a TT and exploration of nodes at least in the central compartment.