The study aims to compare two aspects concerning the diagnosis of acquired immune deficiency syndrome (AIDS)-associated central nervous system (CNS) pathology (neuroAIDS): clinical diagnoses issued ante mortem with pathology results issued post mortem. The group of 39 human immunodeficiency virus (HIV)-positive patients was created over 23 years and is limited by marked heterogeneity. The enrolled cases were treated at the "Prof. Dr. Matei Bals" National Institute for Infectious Diseases, Bucharest, Romania, deceased due to AIDS-related complications and underwent brain necropsies performed in the Pathology Laboratory at the "Colentina" Clinical Hospital, Bucharest. The level of superposition between clinical and the necroptic diagnoses of neurological AIDS-associated diseases was: 60% for progressive multifocal leukoencephalopathy (PML), 50% for cerebral cryptococcosis, 33% for cerebral toxoplasmosis, 20% for cerebral lymphoma, null for cerebral tuberculosis, HIV encephalopathy (HIVE), neurosyphilis and cytomegalovirus cerebral infection. Half of the cases without an AIDS-associated CNS lesion were previously clinically overdiagnosed. We observed that the rate of overdiagnosis concerning an AIDS-associated cerebral illness has risen from 36% in 1993 to 124% in 2015, an elevation with statistical relevance [p=0.037, confidence interval (CI) 95%]. The rate of underdiagnosis has slowly risen from 24% in 1993 to 40% in 2015, however, with no statistical relevance. The rate of clinical confirmation has been stagnant in linear regression from 1993 to 2015. The results of our study reveal a gap between ante mortem and post mortem diagnoses, with many instances of overdiagnosis and underdiagnosis of several major AIDS-associated CNS illnesses, highlighting the need for a more detailed, multidisciplinary approach of neuroAIDS.