Increased neurotoxicity and poor long-term neurocognitive outcome of preschool children treated for brain tumors have led to innovative therapeutic strategies in order to delay or avoid the use of craniospinal radiation and to improve survival. Because these protocols are relatively new, few data exist regarding cognitive outcome. We conducted a twin case-control study to investigate neurocognitive and behavioral outcome in a preschool patient who was 16 months old at diagnosis of medulloblastoma and was treated with surgery, chemotherapy, stem cell transplant, and focal radiation to the tumor bed. Stability and change over two assessments were compared for the patient and her nonaffected twin for standardized measures of cognitive function and experimental measures of parent-child interaction, social competence, and goal-directed play. A striking finding was improvement in intelligence, receptive language, and visual-motor functioning in the affected twin from 12 months to 24 months after treatment. Improvement in ratings of parent-child interaction and social competence for the affected twin was also evident. These findings are notable compared with the potentially devastating impact of craniospinal tumor, and this study is among the first to document the relative benefit of focal radiation in sparing cognitive function, albeit in a single case study.