Patients with childhood relapsed and refractory mature B-cell non-Hodgkin lymphoma (B-NHL) and acute lymphoblastic leukemia (B-ALL) are rare and have a dismal prognosis. The previous UK national analysis of 26 children over a 7-year period prior to 1996 had highlighted the poor outcome, with only three survivors. This 10-year multicenter study evaluated recent data, since 2000. Of 33 children, nine survived (27.3%), with a median follow-up of 4.3 years. On exclusion of six children treated with palliative intent, the survival was one-third (nine of 27; 33.3%). All patients with primary refractory disease (n = 7) and all except one with early relapse (n = 11) died. Administration of four doses of 375 mg/m(2) of rituximab was associated with a longer survival (p = 0.006). Response to reinduction (p < 0.001) and autologous hematopoietic stem cell transplant (auto-HSCT) (p = 0.003) were significant on multivariate analysis. Patients with a time to relapse of at least 6 months are potentially curable and must be offered intensive treatment with salvage chemotherapy, rituximab and auto-HSCT.