Abstract: Human epidermal growth factor receptor-2 （HER2） -positive breast cancer is highly aggressive, with high recurrence rate and poor prognosis. Approximately 50% of patients with metastatic HER2-positive breast cancer will develop brain metastases. In recent years, the emergence of targeted therapy has significantly prolonged the survival of breast cancer patients. However, how to penetrate the blood-brain barrier and improve prognostic effect of breast cancer brain metastasis is still a challenge facing researchers. Here, we reported a case of HER2-positive breast cancer patient with brain metastasis who was resistant to trastuzumab and small-molecule tyrosine kinase inhibitor （TKI） and could not be reached by trastuzumab emtansine （TDM-1）. After multidisciplinary consultation by Department of Breast Surgery, Department of Oncology, Department of Pathology and Department of Imaging, the patient was treated with inetetamab. Throughout the treatment, the patient had stable extracranial lesions and progressive intracranial lesions. Hence, systemic treatment was continued and local treatment intervention was strengthened. The progression of disease was effectively controlled. The diagnosis and treatment of this case suggest that treatment methods for patients with HER2-positive breast cancer with brain metastases should be determined according to the characteristics of brain metastases and extracranial lesions, physical and economic status and previous treatment mode. Multidisciplinary diagnosis and treatment contribute to identifying the optimal individualized treatment and improving clinical prognosis.