We describe a 6‐month‐old infant with classic medulloblastoma. Gross total resection of the left cerebellar tumor was performed; however, relapse occurred during the administration of intrathecal and intravenous methotrexate‐based chemotherapy. After undergoing resection, high‐dose chemotherapy was administered consisting of topotecan, melphalan, and cyclophosphamide with autologous peripheral stem cell rescue followed by local irradiation and intrathecal topotecan, which resulted in a complete response for more than two years. The administration of high‐dose chemotherapy followed by intrathecal topotecan as maintenance therapy is an effective strategy, without losses in the cognitive function, for avoiding the use of whole‐brain irradiation for infantile classic medulloblastoma. Pediatr Blood Cancer 2014;61:2316–2318. © 2014 Wiley Periodicals, Inc.