During the last 15 years, we have used the National Cancer Institute (NCI) 89-C-41 protocol in patients aged younger than 21 years with Burkitt's leukemia/lymphoma (BLL) and diffuse large B-cell lymphoma (DLBCL). According to the Magrath staging system, patients were classified as low and high risk. Low-risk received three cycles of the CODOX-M regimen; high-risk patients received four alternating cycles with the CODOX-M and IVAC regimens. Thirty-five patients entered the study: 32 (91%) achieved complete remission (CR); three were non-responders and died and one patient died in CR. Two responders relapsed after 2 months and one presented early B acute lymphoblastic leukemia 33 months from the end of therapy. The 5-year overall survival and event free-survival are 83% and 80%, respectively. No late toxicity was registered. In our experience with a median follow-up of 11 years, the NCI 89-C-41 protocol has confirmed its high cure rate in BLL and DLBCL children and adolescents.