Poorly differentiated insular carcinoma of the thyroid is a rare thyroid malignancy that is intermediary in biological behavior between well-differentiated and undifferentiated thyroid carcinoma. We used fine-needle aspiration (FNA) to diagnose a poorly differentiated insular carcinoma with unusual cytological features in a 53-yr-old woman with a history of goiter and hypothyroidism, who presented with a massively enlarged thyroid gland and a large liver metastasis. The hypercellular aspirates were comprised predominantly of individually dispersed tumor cells. The tumor cells were small, monotonous, round to oval, and often plasmacytoid with eccentric hyperchromatic nuclei and occasional binucleation; finely granular, ill-defined cytoplasm; and smooth nuclear contours, with hyperchromasia, and small to inconspicuous nucleoli. There were no identifiable microfollicles, necrosis, and mitotic figures. The differential diagnosis included poorly differentiated insular carcinoma, medullary carcinoma of the thyroid, and low-grade lymphoma. Immunocytochemical staining for thyroglobulin, calcitonin, and CD45 yielded negative findings. The insular pattern and scattered microfollicles were appreciated only focally in the specimen from the total thyroidectomy, which also showed other histological patterns including solid, trabecular, and papillary forms. In addition to small, uniform cells, Hürthloid, columnar, and clear cells were focally noted. Thyroglobulin immunoreactivity was recognized only in areas with well-formed follicles. In view of the aggressive nature of insular carcinoma, preoperative recognition is important in planning appropriate therapy. Familiarity with the cytomorphological features, a high index of suspicion, and consideration of appropriate differential diagnoses can greatly aid in reaching a definitive preoperative diagnosis. The limitations of FNA in the sampling of a large tumor with heterogeneous patterns should be kept in mind when interpreting the cytomorphological and immunocytochemical results. Diagn. Cytopathol. 2005;32:103–107. © 2005 Wiley-Liss, Inc.