Endemic Burkitt lymphoma (eBL) is linked to Epstein-Barr virus (EBV) and malaria in Africa, but the risk factors for sporadic childhood BL are not known. In a review of clinically presumed pediatric (< 15 years) BL cases with biopsies and pathology reports at St. Mary’s Hospital, Lacor (Gulu, Uganda), of 88 clinically presumed BL cases clinical diagnostic accuracy of 75% with a possible range of 62-85%, and local pathology diagnostic accuracy of 82% with a possible range of 58%- 88%. Accuracy of clinical diagnosis of Burkitt lymphoma was reduced by inclusion of other diseases with similar clinical presentations. Local pathology, using morphology alone, only marginally improved clinical accuracy and often could not support outside pathology review due to inadequate laboratory procedures. There is an urgent need to improve local pathology prior to conducting high quality clinical and epidemiological studies. Using data from the SEER registry, we are assessing cross-sectional age-specific rates for BL. We have shown two separate peaks among males and females, near ages 10 and 75 years, and a third peak near age 40 years among males. The tri/bimodal incidence pattern was present in sensitivity analyses excluding registries with many HIV/AIDS cases and in period-specific, cohort-specific analyses. Trimodal/bimodal BL suggests heterogeneity in etiology or biology of BL diagnosed at different ages in males and females. A pilot case-control study of Burkitt lymphoma including children aged 0-15 years from Malawi (261 with Burkitt lymphoma and 253 without) from Malawi to investigate the role of humoral immunity to malaria, malaria genotypes, and host malaria resistance genes is on going.