Purpose <p>This report expands the known clinical phenotype of anti-Ri (ANNA-2)-associated paraneoplastic syndrome to include isolated neocortical involvement.</p> Methods and results <p>We report the case of a 54-year-old woman who presented with transient apraxia, confusion, and headache. Brain MRI revealed a tumor-like lesion in the left frontal cortex. Stereotactic brain biopsy showed inflammatory changes without evidence of malignancy. Serum testing was strongly positive for anti-Ri antibodies, and systemic workup identified breast cancer with axillary lymph node metastasis. The patient received breast cancer surgery and chemotherapy alongside high-dose steroid pulse therapy and four weekly doses of rituximab, resulting in marked resolution of the cortical lesion.</p> Conclusion <p>While current PNS-Care diagnostic criteria enabled a definitive diagnosis, further investigation is warranted to elucidate the underlying pathomechanism of cortical involvement in anti-Ri paraneoplastic neurological syndrome.</p>