The original descriptions of medullary carcinoma stressed the lack of papillary and follicular differentiation and the presence of amyloid. During the last few years, the spectrum of histological features seen in tumours of C cell origin has broadened, and papillary and anaplastic forms have been reported. We have recently studied three cases of medullary carcinoma with a major ‘tubular’ or ‘follicular’ component, giving a microscopic picture suggestive of follicular carcinoma of the thyroid. These cases were studied with routine techniques, electron microscopy, and immunohistological methods using antibodies to calcitonin and thyroglobulin. In all three cases the calcitonin localization was positive, and apart from included peripheral thyroid follicles, the thyroglobulin was negativeeven in the tumour with large follicles containing PAS positive colloid. In the cases with tubular lumina, electron microscopy showed a concentration of granules in the apical portion of the cells, with corresponding immunolocalization of calcitonin in a ring about the lumen. We conclude that medullary carcinoma should be considered in the differential diagnosis of every unusual thyroid carcinoma, even those showing glandular differentiation and containing apparent follicles, and that immunolocalization techniques using calcitonin and thyroglobulin are essential for accurate diagnosis of thyroid car