Objective: Although stereotactic brain biopsy has played an important role in the diagnosis and management of brain lesions, there is a significant number of patients in whom a histologic diagnosis is not achieved. The non-diagnostic result of stereotactic biopsy poses a management dilemma. The goal of this study was to analyze the non-diagnostic results after stereotactic biopsy, subsequent management, progress and final diagnosis. Methods: The authors reviewed the clinical and radiological records of 158 patients who underwent stereotactic brain biopsies using Leksell stereotactic frame. We included 138 patients who were followed more than 6 months in this study. Results: The results were diagnostic in 118 cases and the overall diagnostic yield of the procedure was 85.6%. A definite histological diagnosis was not made in 20 patients: gliosis in 10, normal white matter in 5, necrosis in 2, infiltration of inflammatory cell in 2, and insufficient material in 1. The subsequent managements, progress and their final diagnoses were described. Conclusion: Stereotactic biopsy has evolved as a powerful and safe tool to provide tissue diagnoses with minimal disruption of normal functioning brain. Multiple serial biopsy, intraoperative histological diagnosis, and updated imaging-guided biopsy should be tried to minimize the sampling error. Clinical and radiological follow-up are essential for further diagnosis and management in non-diagnostic cases.