BACKGROUND: Paraneoplastic neurological syndrome is an immune-mediated phenomenon where antibodies from tumor cells are produced against neuronal proteins. Amphiphysin antibody is an onconeural antibody linked to the diagnosis of breast cancer and small-cell lung cancer. It is uncommon and typically associated with stiff-person syndrome, of which 90% of patients are eventually diagnosed with breast cancer. CASE PRESENTATION: We present a case of a 47-year-old Caucasian woman with metastatic hormone receptor-positive breast cancer who developed bilateral facial nerve palsy while on treatment with nab-paclitaxel. The patient was found to have anti-amphiphysin antibody in the serum and cerebrospinal fluid. She was treated with methylprednisolone and intravenous immunoglobulin, which resulted in partial improvement in her facial nerve palsy. CONCLUSIONS: This case highlights a rare presentation of bilateral facial nerve palsy that likely related to paraneoplastic syndrome associated with the presence of anti-amphiphysin antibody.