The successful therapy of space-occupying lesions of the brain stem, depends on precise histological diagnosis. Although the clinical management and contemporary imaging techniques (computerized tomography and magnetic resonance imaging) are now able to reveal and approach the diagnosis in these cases, only the combination of these two with the use of contemporary stereotactic systems, is able to secure the precise histological diagnosis for the patient with a good degree of safety. This study presents the first five patients in Greece with space-occupying lesions of the brain stem, in whom a stereotactic biopsy was carried out. All patients were subjected to CT-guided stereotactic biopsy, via the frontal approach in 4 patients with lesions in the superior pons and the mesencephalon and in one patient via the transcerebellar approach, for a lesion in the lateral surface of the pons. Precise histological diagnosis was possible and on the basis of a reliable choice of histological criteria the appropriate therapeutic approach was chosen, thus avoiding the old "empirical" treatment.