Orofacial granulomatosis (OFG), also termed granulomatous cheilitis, oral granulomatosis, and cheilitis granulomatosa, is an uncommon disorder. The presentation can be very varied; pathogenesis is not very clear; and the treatment result is often disappointing. It is characterized by persistent enlargement of the soft tissues of the lip, oral mucosa, and the area around the mouth. Other granulomatous disorders like sarcoidosis, Crohn disease, leprosy, and tuberculosis must be ruled out before making this diagnosis. We describe herein an index case and 4 subsequent cases of idiopathic OFG that responded dramatically and almost completely to treatment with weekly oral azithromycin pulse doses.