<p>Developmental origin and function of thyroid parafollicular or C cells have remained a mystery for a long time. These cells were recognised at the end of the 19th century, their endocrine function in vertebrates shown by the half of the 1900s, and shortly after their source was ascribed to the neural crest. This latter idea was considered valid up to few years ago, when in mammals and man it was shown that they originate from the endoderm, i.e. from the primitive intestine like thyrocytes, and their neuroendocrine differentiation is absent in embryonic progenitors but occurs only when they reach the primitive thyroid bud. Consistently, the thyroid medullary carcinoma arising from C cells has to be considered an epithelial tumour like the intestinal adenocarcinoma and not a neuroendocrine neoplasia. Primary localisation of its metastases is in the pre-laryngeal sentinel lymph node or Delphian lymph node, confirming original observations from the 1800s that parafollicular cells establish key functional contacts with interfollicular lymphatic vessels.</p>