The report on pachyonychia congenita (PC) in NORD’s Rare Disease Database has recently been updated and reviewed by Frances Smith, PhD, chief scientific officer of the Pachyonychia Congenita Project. PC is a rare, keratinizing skin disorder inherited in an autosomal dominant fashion. The predominant characteristics are severe plantar pain, palmoplantar keratoderma including calluses with underlying blisters, and variable hypertrophic nail dystrophy, often accompanied by oral leukokeratosis, cysts of various types, follicular hyperkeratosis, palmoplantar hyperhydrosis, and sometimes natal teeth. PC is normally diagnosed by clinical examination, which can now be confirmed at the molecular level.