Medullary thyroid carcinoma (MCT) is a sporadic or familial tumor of the parafollicular or C-cells that secretes calcitonin. The sporadic form usually presents with a palpable thyroid nodule or cervical adenopathy, by which time basal calcitonin levels are almost always elevated. Without special stains, fine-needle biopsy may fail to detect MCT. Recently, several investigators have recommended routine measurement of serum calcitonin in patients with nodular thyroid diseases for the preoperative diagnosis of MCT. A 31-year-old woman had a large palpable MCT with normal calcitonin and carcinoembryonic antigen levels before surgery. Fine-needle aspiration (FNA) demonstrated atypical cells but was not diagnostic of MCT. Pathology revealed a 3 x 4.5 x 2.3 cm MCT. Immunochemical stains showed immunoreactivity for calcitonin and synaptophysin, but no immunoreactivity to thyroglobulin. Postoperative basal and pentagastrin-stimulated calcitonin levels have remained undetectable without evidence of recurrent cancer. We have evaluated six other patients with MCT that were palpable. They had preoperative calcitonin levels ranging from 322-50,032 pmol/L. This unique case of a woman with a 4.5-cm MCT and normal preoperative calcitonin levels, emphasizes the need for careful clinical evaluation and FNA biopsy in managing patients with nodular thyroid disease.