BACKGROUND: The small cell variant of medullary thyroid carcinoma (SCV-MTC) is a very unusual tumor that carries a poor prognosis. This tumor type closely resembles small cell pulmonary neuroendocrine carcinoma or lymphoma. CASE: A 43-year-old woman had a palpable mass on the right side of her neck. A fine needle aspiration biopsy (FNAB) revealed a hypercellular lesion composed mainly of isolated, small, round cells with salt-and-pepper chromatin interspersed with inconspicuous deposits of fluffy acellular material. A diagnosis of "malignant tumor, consistent with small cell carcinoma, metastasis not excluded" was rendered during the on-site rapid cytologic examination. Immunostaining showed a few isolated cells reactive for calcitonin, intense and diffuse immunoreactivity for carcinoembryonic antigen, dotlike positivity for chromogranin and cytokeratin, and negativity for thyroglobulin. Congo-red staining was positive in the acellular deposit, consistent with SCV-MTC. Subsequent total thyroidectomy confirmed this diagnosis. CONCLUSION: The wide range of cytomorphologic features of MTC can be misleading on FNAB and can be a diagnostic challenge. Congo-red staining and immunoreactivity for calcitonin can be negative in this variant. Consequently, salt-and-pepper chromatin, Congo-red staining and a panel of antibodies comprising calcitonin, carcinoembryonic antigen, chromogranin, cytokeratin, leukocyte common antigen and thyroglobulin are mandatory for the correct diagnosis.