Medullary thyroid carcinoma (MTC) is an aggressive form of malignancy, virtually incurable except by complete surgical resection. With insidious onset and occasional rare clinical variants, it is often diagnosed late in the course of disease and has a poor prognosis. We aimed to evaluate diagnostic efficiency, treatment modalities and outcome in patients admitted to our department between 2004 and 2015, diagnosed with MTC, with emphasis on rare clinical presentations. We identified 28 patients (12 men, 16 women), aged 49.7±16.1 years: seven with MEN2A syndrome, two with familial MTC and 19 with sporadic MTC. Most patients presented for evaluation of a nodular goiter (57%) or for screening if from a MEN2A kindred (14.28%) but the rest showed signs of extensive disease: dysphagia, dysphonia, spinal compression by bone metastases, chronic diarrhea, ectopic Cushing syndrome or a catecholamine crisis in a MEN2A patient. Diagnostic workup confirmed extensive disease: 19 patients (86.3%) were TNM stages III or IV, and calcitonin was >400 pg/ml in 13 patients (20 of 28 with available data the remaining were misdiagnosed preoperatively, leading to inadequate initial surgery and the need for repeat interventions in 46.4%). Precise calcitonin measurement is important in diagnosis and follow-up; however, two cases with metastatic disease presented with normal calcitonin levels, suggesting dedifferentiation. Multiple surgeries were followed in persistent disease by adjuvant therapies: chemotherapy, radiotherapy, somatostatin analogues and IFN. In two patients beyond surgical resources, wide metastatic spread required oncologic evaluation. Management of MEN2A patients was complicated by the need for additional parathyroid and adrenal surgery (thyroid surgery could not be performed in a patient with inoperable bilateral infiltrative pheochromocytomas), by patients reluctance to conform to life-long rigorous follow-up and to undergo thyroid surgery if asymptomatic. At the end of follow-up (79.6±117.4 months) only 37% (ten of 27 patients with available data) had calcitonin <15 pg/ml suggesting cure. Calcitonin testing for selected thyroid nodules might improve diagnostic accuracy and success of surgery.