A 76-year-old woman was referred for 18F-FDG PET/CT assessment of a colorectal cancer. A 9-cm 18F-FDG–avid fatty mass was depicted in the right thigh, suggesting either hibernoma or liposarcoma. Because MRI could not rule out well-differentiated liposarcoma, and biopsy was difficult, surveillance was decided. Follow-up PET/CT showed an increase of 18F-FDG uptake in the fatty mass. We repeated PET/CT after oral administration of 60 mg of propranolol 1 hour before 18F-FDG injection. A dramatic decrease in 18F-FDG uptake was observed, strongly supporting the diagnosis of hibernoma.