Pachydermodactyly is a benign, superficial fibromatosis frequently observed in young males. We describe the condition in two young girls affected by Ehlers-Danlos syndrome (EDS) and tuberous sclerosis, respectively. We hypothesized that in the patient with tuberous sclerosis, pachydermodactyly is a clinical manifestation of the associated systemic disease, whereas obsessive-compulsive behavior is probably the main cause in the girl with EDS.