Although granulomatosis with polyangiitis (GPA) can affect a large number of organ systems and produce a broad spectrum of clinical symptoms, skeletal involvement is very rare, with the exception of facial bone involvement associated with destructive nasal and sinus inflammation. We describe here a 54-year-old man with sternal osteomyelitis and destructive arthritis around the sternoclavicular joint. Despite antibiotics and conventional immunosuppressive treatment, his symptoms deteriorated, and a new mass-like lung lesion was developed. A histopathologic analysis of the lung mass revealed chronic granulomatous inflammation with fibrinoid necrosis, and he was diagnosed with GPA. When a patient with a destructive inflammatory lesion has negative culture results and no response to conventional therapy, we propose that an aggressive approach is necessary for a pathologic diagnosis to exclude the possibility of GPA.