Osteonecrosis of the jaw is a significant complication secondary to radiation therapy or drug therapy, most commonly bisphosphonates. Safety data regarding the administration of bisphosphonates in bone metastatic head and neck cancer patients with history of jaw irradiation are almost non-existent. In this paper, we report the case of a Head and Neck (HNC) patient, with history of radiation therapy to the mandible region, treated with intravenous bisphosphonates for bone metastases that resulted in gross, life threatening mouth hemorrhage secondary to advanced, locally invasive ONJ.