Childhood malignant gliomas are rare and their clinical behavior is almost as aggressive as in adults: they resist treatment, progress rapidly and often spread. Therapeutic strategies at relapse deserve an experimental approach, since none of the conventional-dose treatments have demonstrated a clear superiority over the others and no randomized trials have proved that high-dose chemotherapy is better than conventional treatment. Vinorelbine is a semi-synthetic vinca alkaloid with an in vitro and in vivo experimentally proven broad spectrum of activity, including against malignant brain glioma. We report our experience with a 19-year-old girl with glioblastoma multiforme (GBM) of the deep temporal region recurring 6 months after completing an intensive treatment that included preradiation chemotherapy (chemotherapy as a preradiation "sandwich" phase) with a myeloablative course of thiotepa, tumor bed radiotherapy and postradiation maintenance chemotherapy. The GBM proved fully responsive to intravenous vinorelbine, with a subsequent progression-free interval lasting more than 24 months. This case report suggests that vinorelbine is effective against high-grade pediatric glioma and, since this evidence has only one precedent in the literature (and given the generally poor prognosis for this tumor), even this single success seems worth reporting.