A 42-year-old patient was admitted to our clinic with the diagnosis of primary chronic osteomyelitis of the mandible. Since the initial manifestation, approximately 9 months earlier, the patient had undergone numerous antibiotic treatment trials. Various tissue specimens exhibited no microbial growth. Computer tomography demonstrated severe sclerotic changes with partly osteolytic areas in the complete right horizontal ramus of the mandible. Decortication was carried out and both soft and hard tissue specimens were taken. Histological assessment revealed slightly sclerotic bone with reactive periosteal bone production, as in chronic non-specific osteomyelitis. Because of progressive pain and paresthesia, a 3-phase skeletal scanning was performed before the planned resection. In addition to an intensive labeling in the right mandible, further intensive lesions were found at the first right rib, the sternum, and the vertebral column. The subsequent magnetic resonance tomography confirmed the infiltration, as seen in osteomyelitis, in all these areas. Under the assumption of chronic recurrent multifocal osteomyelitis (CRMO), an immunosuppressive therapy with diclofenac and prednisolone was started, which at first brought about complete remission. As CRMO is very rare in our specialty, it might be suspected that it is the cause of some cases of primary therapy-resistant osteomyelitis. The importance of early diagnosis must be underlined, because therapy differs fundamentally from that of the more common bacterial osteomyelitis. A bone scan is therefore of great value in the diagnostic scheme of therapy-resistant osteomyelitis.