An 84-year-old man presented with acute confusion, global aphasia, and fever. Magnetic resonance imaging (MRI) showed hyperintense lesions on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images predominantly affecting the cortical gray matter of the left mesial temporal and inferior frontal lobes, and insula. Acyclovir was prescribed for presumed viral encephalitis. Clinical and MRI worsening prompted a left temporal lobe biopsy that revealed primary central nervous system lymphoma (PCNSL). This case adds to the MRI spectrum of PCNSL and illustrates that it may mimic the clinical and MRI presentation of herpes simplex encephalitis.