A 49-year-old man was referred to the metabolic clinic for evaluation of severe hypercholesterolemia and xanthomas, which were particularly prominent on the hands. The lesions were painful and affected the patient’s everyday life, making it difficult for him to open bottles or shake hands. He had a 2-year history of biliary cirrhosis due to ischemic cholangiopathy. Laboratory evaluations showed a total cholesterol level of 970 mg per deciliter (25.1 mmol per liter); a triglyceride level of 158 mg per deciliter (1.8 mmol per liter); a low-density lipoprotein (LDL) cholesterol level of 875 mg per deciliter (22.6 mmol per liter), with presence of lipoprotein-X; and a high-density lipoprotein cholesterol level of 64 mg per deciliter (1.7 mmol per liter). Treatment with LDL apheresis was started. Palmar xanthomas can also be seen in patients with type III hyperlipoproteinemia (familial dysbetalipoproteinemia). Xanthomas are rarely so severe that they interfere with activities of daily life. Within 3 months after the initiation of weekly LDL apheresis, the lesions had almost disappeared and the patient reported substantial relief from pain and improvement in function. At follow-up 10 years after presentation, the patient was in stable condition and was undergoing LDL apheresis every other week. Since the initiation of LDL apheresis, his LDL cholesterol level had decreased to 110 mg per deciliter (2.8 mmol per liter).