Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is an extremely therapy resistant osteomyelitis-like disease exclusively involving the jaw bones of patients in treatment with bisphosphonates (BPs). Objectives: The aim of this study was to evaluate the radiological and clinical findings and management of 51 patients with BRONJ diagnosed from 2004 to 2009 in our Reference Center. Study Design: A prospective study was performed. The patients were examined every 2-6 months, depending on their clinical conditions. Outcome variables were the resolution of symptoms, persistence of bone exposure and / or fistula and the status of the lesional mucosa. Results: The higher prevalence of the disease was noted in 2006 and 2007 and at the time of diagnosis 90% of patients had been treated with iv BPs. The main precipitating event leading to BRONJ was an invasive dental procedure in 61% of patients while no traumatic event could be identified in 16% of patients. The median time of follow-up was 19 months (range: 2-57), during which 31% of patients healed and 39% succumbed. In 78% of patients the therapy was medical, in 16% it consisted in surgical deep curettage and only in 6% it was necessary to perform an osteotomy to avoid a mandibular pathological fracture. All the patients in treatment with oral BPs healed from BRONJ with a median time of conservative treatment of 19 months. Conclusions: Prevention has lead to a progressive reduction in the prevalence of BRONJ. In our experience medical treatment is often sufficient to keep the disease under control and to lead to the healing of the lesions by spontaneous loss of the sequestrum. This approach seems to be very effective in patients who were in treatment with oral Bps preparations; BRONJ seems to have a more benign clinical behaviour in these patients.