Background: Epithelioid glioblastoma (eGBM) is a recent addition to the World Health Organization’s classification of central nervous system (CNS) tumors. This rare lesion has a predilection for younger patients, can mimic metastatic disease on preoperative imaging and intraoperative pathology, and portends a poor prognosis due to propensity for leptomeningeal dissemination.

Case Description: We discuss a case of a young woman with a history of ovarian cancer who presented with seizure and a new ring-enhancing left temporal brain lesion. The patient underwent gross-total surgical resection of this lesion, during which frozen section suggested metastasis. However, pathologic interrogation showed pleomorphic epithelioid cells and glial fibrillary acid positivity, suggesting eGBM. The patient has since completed radiotherapy and six-month post-operative imaging has not revealed recurrence or leptomeningeal dissemination.

Conclusion: Our patient's clinical history and pre-operative radiographic evaluation suggested CNS metastatic disease. Ultimately, final pathology revealed eGBM, a newly classified CNS primary tumor. This reinforces the importance of direct tissue sampling and including eGBM on the differential for young patients with histories of systemic cancer presenting with new CNS lesions.