Abstract Mantle cell lymphoma (MCL) and Burkitt lymphoma respond to initial intense therapies, such as hyper-CVAD (hyperfractionated cyclophosphamide/ vincristine/doxorubicin/dexamethasone) alternating with high-dose methotrexate/cytarabine, to which the monoclonal antibody rituximab has recently been added. This report provides an update detailing the long-term outcome when this chemoimmunotherapy regimen is used as first-line therapy for newly diagnosed MCL, de novo Burkitt lymphoma, atypical Burkitt lymphoma, and mature B-cell acute lymphoblastic lymphoma (B-ALL). Ninetyseven patients with de novo MCL and 31 patients with Burkitt lymphoma, atypical Burkitt lymphoma, and B-ALL were treated with rituximab plus hyper-CVAD alternating with rituximab/methotrexate/cytarabine under different institutional trials approved by the University of Texas M. D. Anderson Cancer Center Institutional Review Board. Overall response rate (RR) for patients with MCL was 97% (complete response [CR]/unconfirmed CR rate, 87%). At a median follow-up of 4.8 months, the 5-year failure-free survival and OS rates were 48% and 65%, respectively. Among patients aged ≤ 65 years, the 5 year failure-free survival was 60%. Patients with blastoid morphology have a 7-year survival rate of 47%. Toxicity was mainly hematologic but significant. Overall RR for patients with Burkitt lymphoma/atypical Burkitt lymphoma/B-ALL was 97% (CR rate, 86%). With a median follow-up of 22 months, the estimated 3-year OS, disease-free survival, and event-free survival rates were 89%, 88%, and 80%, respectively. Rituximab plus hyper-CVAD alternating with rituximab/methotrexate/cytarabine is an effective dose-intense chemoimmunotherapy program for untreated MCL, Burkitt lymphoma, atypical Burkitt lymphoma, and B-ALL. Toxicity is mainly hematologic and significant, but expected.