Introduction: The diffuse sclerosing osteomyelitis (DSO) of the mandible is characterized by recurrent pain of the jaw and swelling of the surrounding soft tissues. The final understanding of the etiology of this disease is still unclear. The symptoms seem often to be recurrent. During the last years some promising reports and small series about effective therapy of the DSO with oral or intravenous bisphosphonates have been published.1-5 Case report: We report about a 66 years old patient suffering from DSO in the lower jaw for 5 years. Conservative treatment with antibiotic and hyperbaric oxygen therapy showed no reduction of his complaints or improvement of the radiological findings. We decided to administer the patient a single shot of 4g zolendronate (Zometa®) intravenously. Within 2 days the patient appeared completely free of pain and the long lasting pain medication could be discontinued. Discussion: Bisphosphonates seem to be a promising option to reduce the progress of DSO and to control the clinical symptoms. However, longtime evaluation und follow up of larger case numbers are still necessary to proof the evidence of this treatment approach. Apart from the promising positive aspects of bisphosphonate treatment in patients with DSO, the undesirable side effects, especially the risk of development a bisphosphonate related osteonecrosis of the jaw have to be taken under account. Therefore, intensive information of the patients about this possible risk and the off-label use of the drug are mandatory. References: 1. Urade M, Noguchi K, Takaoka K, Moridera K, Kishimoto H. (2012) Diffuse sclerosing osteomyelitis of the mandible successfully treated with pamidronate: a long-term follow-up report. Oral Surg Oral Med Oral Pathol Oral Radiol. 114(4):e9-12. 2. Kuijpers SC, de Jong E, Hamdy NA, van Merkesteyn JP. (2011) Initial results of the treatment of diffuse sclerosing osteomyelitis of the mandible with bisphosphonates.J Craniomaxillofac Surg.39(1):65-68. 3. Hatano H, Shigeishi H, Higashikawa K, Shimasue H, Nishi H, Oiwa H, Shindo H, Takechi M, Ohge H, Kamata N. (2012) A case of SAPHO syndrome with diffuse sclerosing osteomyelitis of the mandible treated successfully with prednisolone and bisphosphonate J Oral Maxillofac Surg. 2012 Mar;70(3):626-631 4. Hino S, Murase R, Terakado N, Shintani S, Hamakawa H. (2005) Response of diffuse sclerosing osteomyelitis of the mandible to alendronate: follow-up study by 99mTc scintigraphy. Int J Oral Maxillofac Surg. 34(5):576-578. 5- Soubrier M, Dubost JJ, Ristori JM, Sauvezie B, Bussière JL. (2001) Pamidronate in the treatment of diffuse sclerosing osteomyelitis of the mandible. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 92(6):637-640. Keywords: Diffuse sclerosing osteomyelitis, DSO, mandible, bisphosphonates, zolendronate