Neuromyelitis optica spectrum disorder (NMOSD) is a group of inflammatory disease involving the central nervous system. Although most commonly an idiopathic autoimmune condition, NMOSD may also occur as a paraneoplastic syndrome in rare instances. Herein, we report a rare case of a 60-year-old woman with paraneoplastic NMOSD associated with breast cancer. Our findings increase the recognition that NMOSD may present as a paraneoplastic neurological syndrome associated with breast cancer. Our case also raises awareness of an important complication of neurological complications of breast cancer. Early diagnosis of paraneoplastic NMOSD may be imperative for a better prognosis.