OBJECTIVE The current advances in diagnostic and therapeutic modalities and increasing in survival of patients with systemic diseases and immunosuppressive cases have caused to increasing frequency and variety of Central Nervous System neuropathologic processes indicating the necessary need for accurate localization of space-occupying lesions by cytology and histology. This study was aimed to evaluate the usefulness and safety of stereotactic biopsy in histological diagnosis of such lesions. METHODS Of 2081 patients underwent stereotactic biopsy of brain lesions using Riechert-Mundinger system, 158 had multifocal brain lesions, and were enrolled. RESULTS The ages of studied cases were ranged from 2 years to 75 years (Mean age: 41.3 year), 114 were male and 44 were females. Incidence of histopathologic diagnosis of multifocal brain lesions included Astrocytoma grade II (41.3%), Astrocytoma grade I (12.9%), glioblastoma multiform (11.1%), Astrocytoma grade III (10.2%), malignant lymphoma (10.2%), metastasis (4.6%), pilocytic Astrocytoma (2.7%), abscess (2.7%), craniopharyngioma (1.8%) vascular malformations (0.9%), and tuberculosis (0.9%). Mortality due to operation is none. CONCLUSIONS Histopathologic diagnosis of multiple brain lesions is necessary for decision of appropriate management and stereotactic biopsy of brain lesion is a useful and safe method for histological diagnosis.