The association of acanthosis nigricans, skin tags, diabetes mellitus due to insulin resistance, and obesity in adolescents and young adults represents a well defined syndrome. Hyperandrogenism may also be present. The endocrine origin of this condition is beyond doubt. Insulin and insulin-like growth factor-1, and their receptors on keratinocytes are obviously involved in the complex regulations leading to the peculiar epidermal hyperplasia. This condition is unrelated to other types of acanthosis nigricans, including the congenital and the paraneoplastic types. Control of obesity contributes largely to reverse the whole process, essentially by reducing both insulin resistance and compensatory hyperinsulinemia. Several drugs including metformin, octreotide, retinoids and topical colecalciferol (vitamin D(3)) analogs are also beneficial in clearing acanthosis nigricans.