SAPHO syndrome is a disorder characterized by Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis. As the osteoarticular and skin manifestations often do not occur simultaneously and there are no validated diagnostic criteria, the diagnosis can be difficult. Clinical and imaging investigation is necessary to establish the many differential diagnoses of SAPHO syndrome. The etiopathogenesis involves infectious (probably Propionibacterium acnes), immunologic, and genetic factors. Treatment is based on information gathered from case reports and small series, and is related to specific skin or articular symptoms.