Hereditary osteo-onychodysplasia (or nail patella syndrome) is a rare autosomal dominant disease defined by an association of severe characteristics, with a classic clinical tetrad of dysplasia of the fingernails, patellar hypoplasia or absence, presence of iliac horns, and deformities of the elbow, although renal, ocular and neurological involvement may also be present. The main orthopedic complaint of these patients is patellar instability associated with pain and functional limitation. Most of the literature regarding the treatment of NPS-related patellar problems, concerns pediatric population and there is no treatment algorithm defined for adult patients. NPS has a wide range of presentations in skeletally mature patients, and its severity is also very variable. The general practitioner should be familiar with NPS's clinical presentation spectrum, and the orthopedic surgeon with treatment options, in order to provide the most adequate treatment for each patient. Although there is no cure for NPS, several treatments have been useful in the symptomatic treatment of changes in the knees. We describe a rare clinical case of a 47-year-old female patient with NPS who underwent total knee arthroplasty for knee osteoarthritis.