Childhood glioblastoma multiforme (GBM) is uncommon, accounting for 7.2% of the central nervous system tumors in childhood. Their clinical behaviors are almost as aggressive as those in adults, and the 5-year overall survival rate is poor. We describe a case of a 13-year-old boy with GBM. Fourteen months after surgical resection followed by radiotherapy and temozolomide chemotherapy, the patient showed local recurrence. No response to subsequent bevacizumab treatment was observed. To determine correlations of molecular alterations with clinical outcomes in this case, we examined the expressions of Ki-67, MMP-9, MGMT, VEGF, Ras, and p-AKT using biopsies before and after recurrence. Childhood glioblastomas show a distinct biological behavior and probably a different molecular pathogenesis in comparison to the adult ones. Understanding the molecular mechanisms responsible for the formation and progression of the tumors is critical for identification of novel therapeutic targets.