Calcitonin-negative medullary thyroid carcinoma (CNMTC) is a rare subtype of medullary thyroid carcinoma, characterized by normal serum calcitonin levels, which often leads to misdiagnosis or missed diagnosis. The pathogenesis of CNMTC remains unclear and may involve impaired secretion mechanisms or assay-related false negatives. Diagnostic approaches include ultrasound-guided fine needle aspiration cytology, serum CEA and ProGRP measurements, and RET gene testing. Surgical resection remains the mainstay of treatment, while neoadjuvant therapy may be considered in selected cases. This review summarizes recent advances in the understanding, diagnosis, treatment, and prognosis of CNMTC, aiming to provide clinical guidance for better management of this challenging condition.