50 to 70% of all newly diagnosed childhood cancers in Sub-Saharan Africa are due to Endemic Burkitt’s lymphoma (eBL). It occurs mainly in malaria holoendemic areas where the climate supports Plasmodium falciparum mosquitoes and causes year-round malarial infection. eBL risk is highest in children with high antibody titers to both Epstein - Barr virus (EBV) and malaria. The peak eBL incidence in children coincides with peak malarial antibody genetic diversity, which occurs around 5 to 9 years of age. The precise mechanisms by which malaria influences the disease, however, are not well understood. eBL seems disproportionately affect particular tribal groups within malaria holoendemic areas which suggests a genetic component to the disease. Congruently, there are polymorphisms within the CD36 receptor that cluster in particular tribal groups in similar geographical areas and that could provide candidate genetic markers for eBL screening and prevention. CD36 is a cellular surface receptor found on platelets, red blood cells, macrophages, vascular endothelial cell and other cell types. It plays an important role in maintaining general homeostasis or internal cellular balance in organisms. This article reviews what is known about eBL pathogenesis and discusses how research into the role of malarial antibody diversity and CD36 deficiency in eBL risk could lead to viable solutions for eBL prevention in the resource-limited settings that are worst-affected by the disease.