Background: Primary therapy of medullary thyroid carcinoma (MTC) consists of total thyroidectomy and cervico-central lymphadenectomy. Indication for reoperation may be given given, in case of: (a) normal calcitonin but incomplete primary therapy, (b) elevated calcitonin without proven recurrence, (c) elevated calcitonin with proven recurrence. Methods: We discuss the extent of an adequate reoperation according to primary tumor stage and proven recurrence with special regard to four-compartment lymphadenectomy (FCLA). Results: Medullary thyroid carcinoma metastasizes very common lymphogenously into the cervicocentral compartment (primarily ca. 60%). But in case of proven tumor involved lymph nodes, incidence of lymph node metastases in the cervicolateral (ca. 40 to 60%) and mediastinal (ca. 40%) compartments is very high, too. In contrast do other surgical techniques FCLA removes all locoregional lymph-node compartments systematically. Due to the high incidence of lymph node metastases who might fail pre- or intraoperative detection this systematic technique should be preferred. Conclusions: New surgical techniques and a well defined strategy enable to cure about 25% of patients with medullary thyroid carcinoma biochemically. FCLA is an adequate therapy in case of proven or suspected lymph node metastases.