Two cases of primary oat-cell carcinoma of thyroid, in a 63-year-old woman and a 73-year-old man, are described. Case 1 was a compound tumour with the oat-cell component merging with a papillary component. Both tumours, in addition to histological features consistent with oat-cell carcinoma, showed immunohistochemical positivity with anti-chromagranin A and anti-synaptophysin antisera. Negative results were obtained when anti-calcitonin and anti-thyroglobulin antisera were employed. Using in situ hybridization, chromogranin A and B messenger RNAs were localized with biotinylated oligonucleotide probes. In contrast, with in situ hybridization, no localization for calcitonin messenger RNA was seen using radioactive and biotinylated probes. It is concluded that these calcitonin-free, small-cell carcinomas should be considered separately from medullary thyroid carcinomas and be regarded as a distinct entity, probably the thyroid equivalent of oat-cell carcinomas of the lung. © 1990 Springer-Verlag.