BACKGROUND: Obtaining a definitive pathological diagnosis from brain tissue sampling was challenging due to the small, nonrepresentative sample. This study introduced a novel syringe technique for brain biopsy aimed at enhancing diagnostic accuracy by obtaining core tissue samples that better represent the targeted tissue. METHODS: The 10 patients with atypical brain lesions underwent the syringe biopsy. After meticulous preoperative planning with neuronavigation, a minimally invasive approach was used: a 3-cm skin incision and a 14-mm burr hole were created. A modified 3-cc syringe was used to create negative pressure and cannulate the brain tissue. The desired sample size (24 cm³) was obtained by controlling the syringe depth and withdrawal. Medical records were reviewed to assess sample analysis results and any complications. RESULTS: The syringe technique successfully yielded adequate tissue samples in 9 of 10 patients. In 1 case, the desired tissue could not be retrieved and required a microsurgical approach for removal. In all 10 cases, a correct diagnosis was made without significant complications. CONCLUSIONS: The preliminary findings suggest that the syringe technique is both safe and effective for obtaining substantial volumes of brain tissue, facilitating accurate pathological evaluation in cases of complex neurological disorders.