Introduction: Stereotactic biopsy of brain stem lesions in children evolved from a controversial background but the current trend seems towards a safe procedure that will yield diagnostic accuracy to guide targeted and individualized treatments. Aims and Objectives: To confirm safety, accuracy and usefulness of biopsy of brain stem lesions using our institutional experience on two index cases that underwent stereotactic procedures. Methodology: A review of two case reports were conducted to expose diagnostic success and procedure-related highpoints. Results: In both cases presented the procedure was uneventful, yielded the desired diagnostic tissue and there were no procedure related complications. Conclusion: Stereotactic biopsy of pediatric brain stem lesion is safe. Tissue sampling was accurate in both cases and served as a prerequisite more targeted oncology referral and potentially individualized treatment.