Presented herein is a case of diffuse fatty infiltration of amyloid goiter in a 58-year-old woman with chronic renal failure. Bilateral total thyroidectomy was performed due to symptoms of dysphagia and hoarseness. Macroscopic and microscopic examination showed that almost all thyroid follicles were replaced by fat cells. Hyalinized stroma intervening the fatty infiltration was shown to harbor amyloid deposition.