✓ Malignant glioma is the most common primary brain neoplasm, but generally it is not included in the differential diagnosis of enhancing lesions of the central nervous system (CNS) in patients suffering from acquired immunodeficiency syndrome. We report a case of glioblastoma multiforme (GBM) in a 29-year-old man with human immunodeficiency virus (HIV). Primary CNS lymphoma was suspected, making a definitive histological diagnosis crucial. An initial stereotactic biopsy sample was insufficient to establish a diagnosis and a second biopsy of the lesion was obtained. The histopathological investigation confirmed GBM and adjuvant external radiation treatment was given to the patient, who survived for 4 months after the initial biopsy. A decline in the rate of Toxoplasma infection and the changing diseases observed in HIV infection indicate the importance of obtaining a biopsy in cases of CNS mass lesions.