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Medullary thyroid carcinoma (MTC) is a malignant tumor of the parafollicular cells, which produce calcitonin. As a result, calcitonin is an important tool for diagnosing MTC. When there is focal or no calcitonin staining, diagnosis of MTC can be challenging as this may suggest differences in cell origin and in prognosis and recurrence of the disease. The prognosis and guidelines for management and follow up for MTC remain inconclusive. Here, we present a case of primary neuroendocrine tumor of the thyroid gland with only focal calcitonin staining on immunohistochemistry and low serum calcitonin level despite a tumor size of almost 4 cm. The assumption of C-cell origin was made from positive staining for carcinoembryonic agent (CEA), thyroid transcription factor 1 (TTF-1) and paired box 8 (PAX8) without expression of thyroglobulin (Tg). The patient underwent thyroid lobectomy and follow-up monitoring with ultrasound and measurements of calcitonin and CEA levels, without any further surgical intervention. Few cases of neuroendocrine tumors with limited calcitonin expression have been published and the etiology and prognosis are still unknown. Our case suggests that limited calcitonin expression cannot completely exclude the diagnosis of MTC. This rare type of MTC should be differentiated from the typical presentation of MTC. Treatment and post-operative surveillance should be tailored based on the individual.

Case report of a neuroendocrine tumor of the thyroid gland with limited calcitonin expression: a diagnostic challenge