Medullary thyroid carcinoma (MTC) is a thyroid neoplasm with evidence of C-cell differentiation that accounts for approximately 2% to 3% of all thyroid malignancies. Approximately 70% of MTCs are sporadic, whereas the remainder are heritable and occur as a component of the multiple endocrine neoplasia type 2 syndromes. Multifocal primary C-cell hyperplasia is the precursor of the familial cases. In the past several decades, there have been remarkable advances in the understanding of this tumor type and its precursor lesions at the clinical, histopathologic, and molecular genetic levels. This article presents an update on MTC and C-cell hyperplasia in the context of the 2017 World Health Organization Classification of Endocrine Tumors.