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Stereotactic microsurgical techniques allow for the precise localization and resection of lesions in critical areas of cortex or deep within the brain and minimize operative exposure to the surrounding tissues. This study presents our experience with CT-guided stereotactic microsurgical resection of cerebral lesions using the Leksell frame. A total of 42 patients undergoing computerized tomography guided stereotactic microsurgical resection of cerebral lesions between June 2000 and September 2017 were included in the study. Clinical, radiological, histological and follow-up data were retrospectively evaluated. Pre-and post-operative general status of the patients was assessed by Karnofsky Performance Scale (KPS). Except for the subjects with high-grade gliomas, complete resection could be accomplished in all cases. Of the 24 cases with convulsions, a complete cessation of epileptic attacks was attained in 20 and a decrease in their number and frequency was noted in 4 cases. Overall, 20 patients had no change in the KPS score, while 28 patients had increased and two had decreased KPS scores. No postoperative mortality occurred. CT-guided stereotactic microsurgical craniotomy is a safe, reliable and effective technique, which is particularly useful for the surgical treatment of small, benign cranial lesions and cerebral metastases. © 2018, Logos Medical Publishing. All rights reserved.