Background: Pediatric patients with non-Hodgkin lymphoma (NHL) in developing countries (DCs) present with greater tumor load even at lower stages and with comorbidities that impact therapy delivery. This causes toxic mortality with "standard" intensive protocols or recurrences with "gentler" treatment. Objectives: We developed and evaluated a risk stratification schema that guides intensity of therapy. Design/Methods: Sixty-nine patients were prospectively assigned to five risk groups (A-E; n = 6, 15, 16, 15, and 17) following staging and treated with protocols of risk-stratified intensity. Risk stratification utilized St. Jude stage, disease bulk, and sites involved. Results: Between 2006 and 2011, 69 patients with B-cell NHL were enrolled. Among these, 72.5% were boys with mean age of 6.9 years (+/- 3.33 [SD]; range 2.4-14.2 years). Eighty-seven percent had Burkitt lymphoma, 82.6% had advanced stage (25 [36.2%] stage III; 32 [46.4%] stage IV), and 24.6% were central nervous system positive. Mean lactate dehydrogenase increased progressively across the risk strata. Among these, 0/6, 1/15, 3/16, 2/15, and 7/17 patients relapsed/progressed within each risk stratum. Fifteen patients died; three from treatment-related toxicity. At a median follow-up of 6.2 years, the overall and event-free survival (EFS) for all patients was 78.1 and 75.4%, respectively; EFS was related to risk assignment. The frequency of documented infectious and noninfectious toxicities increased with higher risk group assignment causing prolongation of admissions and potential treatment delays. Conclusions: Reduction in treatment intensity for an identified subset of patients with NHL is feasible, while high-intensity therapy is required for high-risk groups. This risk stratification system may be a first step toward improving the outcomes in some DCs.