Herpes encephalitis superimposed on an intracranial malignancy has previously been described mainly in the context of malignancy imitating infection or in the postoperative setting after neurosurgical intervention. We report a rare case of de novo presentation of concurrent herpes encephalitis and glioblastoma. A 63-year-old man presented with status epilepticus and subsequent magnetic resonance imaging (MRI) brain showed a right temporal enhancing lesion with mass effect. He underwent a craniotomy and debulking of this lesion, which on subsequent histology was positive for herpes simplex virus (HSV) antigens and HSV DNA was confirmed by polymerase chain reaction analysis. The sample however also had some hypercellular areas with atypical astrocytes. Our patient recovered well from surgery and was eventually commenced on acyclovir albeit with a delay of 3 weeks due to the initial diagnostic dilemma. However, he re-presented with lethargy and confusion a further 3 weeks later and an MRI scan showed recurrence of the temporal lesion with MR spectroscopy more suggestive of high-grade glioma. He, therefore, underwent a further debulking surgery and the histology revealed a WHO Grade 4 glioblastoma with some residual areas of inflammation. A diagnosis of 2 co-existing pathologies namely HSV encephalitis and glioblastoma was thus reached. Unfortunately, due to poor performance status, he could not undergo chemo-radiotherapy and died 8 months after presentation. Immuno-modulators, expressed locally and globally in glioma patients, are likely to render them susceptible to infections. There are an increasing number of reports of HSV encephalitis in the glioma setting postoperatively. However, we report a de novo presentation which has only been recognized once before in the 1970s. Recognition of HSV encephalitis in glioma patients in the de novo and also the postoperative context is important for commencing early treatment and preventing poor outcomes.