Medullary thyroid carcinoma (MTC) is a very rare malignancy, which arises from parafollicular C cells and accounts for 3-5% of all thyroid cancers. MTC represents a neuroendocrine tumor with a biology that differs considerably from differentiated thyroid cancer. Presence of a RET proto-oncogene germline mutation indicates hereditary C cell disease in the context of multiple endocrine neoplasia type 2 and hence a special treatment algorithm is required. Cure of MTC is only possible through surgery. Calcitonin screening is advocated for early MTC diagnosis and preoperative MTC management stratification. In case of surgically incurable persistent MTC, estimation of calcitonin and CEA doubling time is crucial to assess tumor biology and is complemented by multimodal imaging to assess tumor burden. Treatment decisions in incurable MTC must be carefully balanced with treatment-related morbidity, since MTC may take an indolent course over years.