Macrofollicular variant is a rare variant of papillary thyroid carcinoma. Although they are usually associated with a good prognosis, aggressive forms have been described. Distinction from an adenomatous goiter or follicular adenoma is often difficult and can lead to misdiagnosis. We report a metastatic macrofollicular variant of papillary thyroid carcinoma with a remarkable clinical, biochemical, and structural response to radioiodine treatment.