Objective <p>This study aimed to evaluate the safety, efficacy, and outcomes of stereotactic biopsy for deep-seated brain lesions. We also assessed the complications and functional results associated with this technique.</p> Methodology <p>We analyzed 56 patients who underwent Leksell G frame-based biopsy at the Punjab Institute of Neurosciences between 2022 and 2024. An exemption letter from the institute’s review board was obtained before data collection. This case series included only patients treated by a single surgeon to reduce the inter-operator variability. Data were collected retrospectively for all consecutive cases.</p> Results <p>Stereotactic biopsy provided accurate diagnostic tissue acquisition with accuracy rate of 94.5%. Complications such as hemorrhage occurred in up to 8% of cases, with mortality rates ranging from 0% to 4% and morbidity rates from 0% to 13%.</p> Conclusion <p>Stereotactic biopsy remains crucial in modern neurosurgery, offering accurate diagnoses with minimal complications, especially for deep, small, multifocal, or diffuse lesions. This technique is a safer alternative to craniotomy with a favorable efficacy and safety profile.</p>