Polycystic ovary syndrome (PCOS), recently renamed as polyendocrine metabolic ovarian syndrome (PMOS), is a common endocrine condition with reproductive, metabolic, dermatological and psychological features, affecting around 10–13% of women worldwide. HAIR-AN syndrome, an unusual multisystem disorder defined as a coexistence of hyperandrogenism (HA), insulin resistance (IR), and acanthosis nigricans (AN), is a rare and severe subtype of PCOS/PMOS. Patients with HAIR-AN syndrome tend to experience more severe form of insulin resistance compared to women with typical PCOS, and obesity is also more prevalent and severe in this group of patients. As one of the most under-diagnosed clinical entities in endocrinology, more research on the molecular mechanisms and cellular events contributing to the pathogenesis of HAIR-AN is required to be able to develop novel treatment strategies for women with this rare subtype of PCOS/PMOS.