We report a case of 70-year-old man with glioblastoma presenting as acute encephalitic illness. The patient exhibited sudden onset of cognitive impairment and headache for 2 days. Initial brain MRI showed left temporal lobe hyperintensity, and cerebrospinal fluid cytology revealed a mild pleocytosis. The patient had initially improved after medical treatment with a presumptive diagnosis of herpes simplex encephalitis (HSE). After 8 months, the patient complained of recurrent seizures. A follow-up brain MRI revealed marked increases in size and surrounding perilesional edema in the left temporal lesion on T2-weighted images and a new contrast-enhancing lesion on gadolinium-enhanced T1-weighted images. Stereotactic brain biopsy revealed a glioblastoma. The atypical encephalitic presentation of glioblastoma should be considered if definitive evidence for the diagnosis of HSE cannot be obtained.