A 30-year-old man had a diagnosis of aggressive carcinoma showing thymuslike differentiation (CASTLE disease) and underwent thyroidectomy for tumor resection and bilateral cervical lymph node dissection. Multiple hypermetabolic nodal metastases were detected in the neck and upper mediastinum with fluorine-18-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography ((18)F-FDG PET/CT). The patient received radiation therapy and chemotherapy for treatment of metastases. Follow-up (18)F-FDG PET/CT demonstrated resolution of several hypermetabolic lesions previously seen in the neck, but innumerable new hypermetabolic metastatic lesions were visualized. The patient died of this aggressive CASTLE disease despite treatment with surgery, radiation, and systemic chemotherapy.