BACKGROUND Thyroid carcinomas historically have been divided into two groups according to their presumedly separate embryonic origins: those of neuroectodermal derivation (parafollicular or medullary carcinoma [MCT]) and those of foregut endodermal origin (follicular and papillary carcinomas). The validity of this concept has been questioned by the recognition that some MCT may show immunocytochemical and ultrastructural evidence of follicular components, and display features of follicular function (e.g., organification of iodine, immunoreactivity for thyroglobulin). METHODS A 14-year-old boy presented with the physical features of multiple endocrine neoplasia type 2-B (MEN 2B) and a thyroid mass. His thyroid lesion was studied by light microscopy; electron microscopy; immunohistochemistry using antisera to calcitonin, thyroglobulin, and other peptides; and in situ hybridization. RESULTS The tumor was identified as an MCT by light microscopy. It stained positively with calcitonin, thyroglobulin, chromogranin, neuron-specific enolase, and serotonin. At the ultrastructural level, the tumor cells contained numerous neurosecretory granules and showed evidence of follicular differentiation (luminal microvilli, follicle formation, and tight junctions), suggesting a dual neuroendocrine and follicular differentiation. CONCLUSIONS The morphologic findings suggest that a small number of MCTs arise from a common stem cell (possibly the ultimobranchial body) that may give rise to both MCT and follicular carcinoma. This patient and patients in similar cases documented in the literature challenge the classic concept of separate pathways of embryogenesis for these two cell types.