C cell hyperplasia and occult medullary carcinoma of the thyroid in asymptomatic individuals at genetic risk can be detected by measurement of serum calcitonin concentrations before and after stimulation with a secretagogue. Electron microscopy was used to confirm the presence of C cell hyperplasia afte demonstration of elevated serum calcitonin values in three asymptomatic young women from two affected kindreds. Nodules of hyperplastic cells were observed in each of the three thyroids and were composed of two types of cells, one rich in secretory granules and the other in mitochondria. In one thyroid relatively large nodules also contained extracellular deposits of amyloid. Although the presence of the two types of cells and amyloid deposits is characteristic of medullary carcinoma, there was no evidence that the C cell nodules were malignant. However, such nodules may represent a certain stage in the development of medullary carcinoma of the thyroid. We believe, therefore, that electron microscopy can demonstrate incipient C cell neoplasia in needle biopsy specimens. Confirmation of C cell neoplasia is desirable for positive diagnosis and hence for genetic counseling in patients with a family history of the disease.