Introduction Central nervous system (CNS) lesions are rare and histologically heterogenous, and carry serious potential for patient morbidity and mortality. A retrospective epidemiological review of CNS neoplasms is of great importance for future research because it can demonstrate the changes in the spectrum of CNS lesions of a population, unveil the possible associated risk factors, and indicate the potential therapeutic methods for various neoplastic and non-neoplastic lesions. Neurosurgeons have always shown an obsession with a good neuropathological diagnosis in intracranial and extracranial lesions. This obsession need not be overemphasized as it helps the clinician plan an adequate surgical/treatment strategy to optimize outcomes and minimize morbidity. Methods This study included a spectrum of 160 biopsies of patients with space-occupying lesions of the CNS during a period of two years (2019-2021). All the cases were studied and analyzed, and their histological typing/grading was done. The cases were graded and categorized according to the 2016 WHO Classification of CNS Tumors. Results Among 160 cases, the study showed a slight male preponderance of 100 (62.5%) cases. The maximum number of cases, 37 (23%) cases, was in the age group of 41-50 years. Clinically, the commonest complaints were headache and seizures. The most common location of tumor was supra-tentorial, comprising around 96 (60%) cases, of which 27 (28%) cases were located in the frontal lobe. There were four (2.5%) cases that had non-neoplastic lesions and the rest 156 (97.5%) cases had neoplastic lesions. Malignant lesions outnumbered the benign lesions, comprising of 82 (51.25%) cases. Among the neoplastic lesions, the highest cases were of astrocytoma, 48 (30.76%) cases, followed by meningioma, 42 (26.92%) cases. Also, 21 extremely rare and unusual cases were encountered. Conclusion The present study reflects the diversity of histopathological spectrum of CNS lesions in our center. In-depth studies from across various hospitals are required to have representative data on the incidence, epidemiological profile, and etiology of CNS lesions in India.