Primary hypertrophic osteoarthropathy, or pachydermoperiostosis (PDP), is an infrequent genetic condition characterized by digital clubbing, periostosis, and pachydermia and is distinct from a more common form, secondary hypertrophic osteoarthropathy, which always associates with an underlying cause (frequently pulmonary or cardiac disease). The diagnosis of this disorder as well as its clinical evaluation can be difficult. We report a 15-year-old boy presenting with intermittent arthralgias and clubbing of fingers and toes for the previous 2 years. The ankles and knees were enlarged, and X-rays showed periosteal apposition. The search for a secondary cause was negative. The skin appearance was normal, but a skin biopsy was indicative of pachydermia, further confirming the diagnosis of PDP. Bone turnover markers were increased at diagnosis and progressively decreased during follow-up; prostaglandin E(2), a recently implicated mediator of this disorder, was markedly elevated. In the present case, carrying out a skin biopsy helped us to diagnose this condition. In addition, bone turnover markers were useful for monitoring the disease activity; whereas, increased prostaglandin E(2) levels seems to confirm the role of this mediator in the etiopathogenesis of this disorder.