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BACKGROUND: Medullary thyroid carcinoma is a rare tumor and represents less than 5% of all thyroid cancers. Tumor size and the presence of possible metastases are strictly related to serum calcitonin level, which also suggests prognosis. A serum calcitonin level above the normal range is highly suspicious for medullary cancer. This tumor has no characteristic patterns on ultrasound and fine-needle aspiration, so serum calcitonin level is the only significant element for diagnosis. The literature contains 47 cases of serum calcitonin-negative medullary thyroid cancer with heterogeneous behavior, ranging from non-aggressive to aggressive form. CASE REPORT: We report a rare case of a young man with negative serum calcitonin but with lateral cervical node metastases from medullary thyroid carcinoma. At the beginning, diagnosis was not achieved due to normal range of serum calcitonin and a negative thyroid ultrasonography for large nodules. Nevertheless, in another medical center he underwent a neck biopsy of the lateral cervical mass. The histologic findings showed metastases of medullary thyroid cancer. Therefore, a total thyroidectomy plus cervical lymphadenectomy was performed. During the follow-up, due to unusefulness of serum markers, and as CEA levels were negative pre- and post-operatively, an ¹⁸F-DOPA PET scan was performed. In 3 years of follow-up, there is still no evidence of disease relapse. CONCLUSIONS: Our case shows how a normal serum level of calcitonin cannot exclude medullary thyroid cancer. Early diagnosis is crucial because it influences appropriate surgical therapy and patient outcome. The current lack of an optimal strategy for the diagnosis and postoperative follow-up for patients with negative serum calcitonin tumor presents a diagnostic challenge for physicians. [ABSTRACT FROM AUTHOR]