Acanthosis nigricans is well recognized in its clinical association with several types of insulin-resistant syndromes, and skin involvement is usually unresponsive to local treatment or management of diabetes. A young woman with a lipodystrophic form of diabetes, hypertriglyceridemia, and severe generalized acanthosis nigricans was placed on a diet with fat supplementation in the form of omega-3-fatty-acid-rich fish oil. She was observed to have striking improvement in the appearance and extent of acanthosis nigricans while receiving this regimen. This occurred despite continued therapy with niacin (nicotinic acid), an agent associated with acanthosis nigricanslike skin changes.