Anaplastic thyroid cancer (ATC) is the type of thyroid cancer that has the worst prognosis. It usually presents as a rapidly growing cervical mass that generates compressive symptoms. Its association with thyrotoxicosis is rare. A 76-year-old woman, with no contributory history, presented with a 3-month course of fast-growing cervical tumor, associated with tenderness, cough, and weight loss. Physical examination revealed goiter, localized erythema, and a painful and stone tumor dependent on the right thyroid lobe. Due to the malignant findings of the thyroid ultrasound, the patient underwent a thyroid core needle biopsy, which indicated ATC. Laboratory tests revealed leukocytosis, decreased thyroid-stimulating hormone, elevated free thyroxine (fT4), and increased thyroperoxidase (TPO) antibodies. At the beginning, we considered that the etiology of thyrotoxicosis was secondary to subacute thyroiditis (SAT) after SARS-CoV-2 infection, due to the immunochromatography result and chest tomography findings. The result of markedly elevated TPO antibodies left this etiology more remote. Therefore, we suspected Graves’ disease as an etiology; however, thyroid histopathology and ultrasound did not show compatible findings. Therefore, we suspect that the main etiology of thyrotoxicosis in the patient was the destruction of the thyroid follicles caused by a rapid invasion of malignant cells, which is responsible for the consequent release of preformed thyroid hormone. ATC is a rare endocrine neoplasm with high mortality; it may be associated with thyrotoxicosis, whose etiology can be varied; therefore, differential diagnosis is important for proper management. Learning points: •• Anaplastic thyroid cancer is the thyroid cancer with the worst prognosis and the highest mortality. •• The association of anaplastic thyroid cancer with thyrotoxicosis is rare, and a differential diagnosis is necessary to provide adequate treatment. •• Due to the current pandemic, in patients with thyrotoxicosis, it is important to rule out SARS-CoV-2 as an etiology. •• Anaplastic thyroid cancer, due to its aggressive behavior and rapid growth, can destroy thyroid follicular cells, generating preformed thyroid hormone release, being responsible for thyrotoxicosis.