Rationale: Medication-related osteonecrosis of the jaw decreases quality of life of patients with cancer. The debate about it continues regarding the risk factors, etiology, and treatment methods, and so on. Also, spontaneous regeneration of the mandible is clinically rare. Patient concerns: A 67-year-old woman presented to the authors’ department complaining of pain, swelling, and pus discharge from a fistula. She previously had breast cancer bone metastases and had received antiresorptive intravenous bisphosphonate. Diagnosis: The patient was diagnosed with medication-related osteonecrosis of the jaw. Interventions: She received conservative therapy with antibiotics and surgical therapy as sequestrectomy under general anesthesia; however, the lesion did not heal. Thirty months after the MRONJ diagnosis, when she was 70 years’ old, she underwent a left hemimandibulectomy without reconstruction under general anesthesia. Outcomes: Spontaneous regeneration of the mandible was observed by follow-up imaging examinations. The patient has no current subjective or objective symptoms. Lessons: This is the first case report of the spontaneous mandibular regeneration after surgery for medication-related osteonecrosis of the jaw. Additionally, this case was the oldest patient among the published mandibular regeneration cases.