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Osteonecrosis of the jaw (ONJ) is a rare and severe necrotic bone disease reflecting a compromise in the body's osseous healing mechanisms and unique to the craniofacial region. Radium 223 dichloride (Ra223) is the only targeted alpha therapy able to extend survival in patients with bone metastases from prostate cancer. Mechanism of action and data currently available focused mainly on osteoblastic metastases from prostate cancer. In 2018, a Caucasian 54-year-old woman presented to our institution for a breast cancer with bone metastases. Since the patient refused any treatment and taking into account the bone disease, our multidisciplinary team evaluated a supplementary strategy with radium 223. A total of six treatments were planned with a dose of 50 KBq/kg every 4 weeks according to Phase 2 data. Four days after the second cycle administration, the patient presented for examination with a self-extracted necrotic bone fragment. Oroantral communication remained in the absence of algic symptomatology or suppuration. The multidisciplinary approach between oncologists, nuclear physicians, and dental health teams is crucial throughout the treatment process to avoid unnecessary suffering in patients at risk. More prospective studies are needed; however, considering the limitation of the present case, radio 223 may play an adjuvant role in the medical treatment of cancer patients with active ONJ.