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Glioblastoma is one of the most aggressive malignancies, and can present with atypical clinical and radiological features, resulting in delays in diagnosis. We report a case of glioblastoma multiforme, presenting with atypical radiological features mimicking herpes encephalitis. The patient was eventually diagnosed with glioblastoma after a brain biopsy with histopathological and molecular testing. We highlight and discuss diagnostic challenges and other supportive diagnostic tools when considering glioblastoma.