Aim of the study. To present a clinical observation of a combined brain tissue lesion in a patient with HIV infection, which emphasizes the complexity of the differential diagnosis process when making a final diagnosis, the need for interdisciplinary interaction of trained specialists.Materials and methods. The description of clinical observation, results of instrumental diagnostic methods is performed. The data of histological and immunohistochemical examination of the biopsy of the patient’s brain tissue are presented.Results and conclusion. Damage to the central nervous system in patients with HIV infection is characterized by a wide range of etiological factors. Diagnosis, in this case, is a complex task and requires a comprehensive examination of the patient, including performing computed tomography, magnetic resonance imaging of the brain, as well as cultural and molecular genetic methods of studying cerebrospinal fluid. Pathognomonic clinical manifestations and neuroradiological syndromes do not exist, and several pathogens can be released simultaneously in the biological fluids of the patient. In addition to determining the etiology of the infectious process, it is necessary to exclude a brain tumor lesion with possible biopsy, histological and immunohistochemical verification of the neoplasm.