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Medullary carcinoma accounts for about 5% of all thyroid malignancies. The tumor may produce other hormones in addition to calcitonin that typically occurs in the presence of distant metastases. The aim of this report is to present a case of invasive medullary thyroid carcinoma producing ACTH and serotonin. A male patient sought medical attention due to facial plethora and distal paresthesia. On thyroid ultrasound, he presented a hypoechoic nodule measuring 6.7 × 3.2 × 3.5 cm, with punctate calcifications and central vascular pattern. The chest computed tomography showed an extensive solid lesion with epicenter in the superior mediastinum and absence of a cleavage plane with the left thyroid lobe. The lesion extended from the glottic area to the lower portion of the trachea and invaded esophagus, posterior tracheal wall, and left jugular. The patient presented hyperglycemia, hypokalemia, increased free urinary cortisol, calcitonin, ACTH and 5-hydroxyindoleacetic acid levels. The nodule cytological examination obtained by fine-needle aspiration was inconclusive, and the open biopsy confirmed the diagnosis of medullary thyroid carcinoma. Due to the advanced disease stage and increased risk of large caliber vessels injury in case of surgery, local chemotherapy and radiotherapy were recommended. With this report, we want to draw attention to an unusual association between advanced medullary thyroid carcinoma with an aggressive course and ectopic production of ACTH and serotonin.