A 27-year-old male without significant past medical history presented following collapse resulting from a syncopal episode at work. There was an episode of vomiting, and one of tonic-clonic seizure activity, which was spontaneously resolved after approximately one minute. His neurologic exam was nonfocal, with full strength in the bilateral upper and lower extremities, and no sensory deficits were elicited. MRI studies demonstrated a 4.7 cm rim-enhancing cystic mass in the right temporal-parietal region, with resultant mass effect and edema. At surgery, intraoperative pathologic consultation favoured a primary glial neoplasm. Subsequent complete histologic examination on permanent sections confirmed the presence of glioblastoma, with a morphologic pattern and immunohistochemical profile most consistent with epithelioid glioblastoma (WHO grade IV). Epithelioid glioblastoma is a rare, especially aggressive variant of IDH-wildtype glioblastoma, recognized in the 2016 World Health Organization classification. Approximately 50% of such tumors harbour the BRAF V600E mutation, which has also been observed in some melanomas where selective inhibitors have demonstrated a therapeutic role. The especially aggressive behaviour and poor clinical outcome typically observed for this variant of glioblastoma demonstrate the importance of emerging areas relevant to neurooncology, specifically those of proteomic characterization and therapeutic nanomedicine.