Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children. Second neoplasms as late effects of therapy for ALL have been recognized as a significant clinical issue given the increasing number of long-term survivors of ALL, because they can be the cause of death in such cases. In contrast, glioblastoma (GBM) is the most common primary brain tumor in adults. It is a malignant brain tumor that most often occurs in elderly patients, and GBM in young adults or adolescents appears to be rare. Here, we describe our experience of two cases of GBM in young long-term survivors of ALL, and emphasize the necessity of careful follow up of patients treated for ALL for the potential occurrence of central nervous system second neoplasms, especially when the patients have previously undergone cranial radiotherapy.