Chronic nonbacterial osteomyelitis is a rare entity of unknown etiology and most likely an autoinflammatory disease. A 45-year-old man complained of a growing painful mass of the right chest wall. FDG PET/CT demonstrated a large destructive rib lesion with intense uptake and extensive FDG avid lymphadenopathy, which mimicked a malignant or metastatic disease. Both CT guided core-needle and excisional biopsies showed reactive/regenerative/granulomatous changes coupled with focal neutrophils and marrow atrophy, consistent with chronic osteomyelitis. Stains and cultures of surgical and wound specimens and multiple blood cultures were all negative for any kind of microorganism.