Burkitt lymphoma accounts for approximately 50% of pediatric cancers in equatorial Africa and a majority of NHL in Uganda. The aim of the study was to examine the expression profile of the RB (pRb2 or p16) and p53 (p53, p14, or p21) pathways in biopsies of endemic BL, and compare it to the pattern found in reactive lymphoid hyperplasia (RLH). A total of 51 BL and 10 RLH biopsy specimens were included in the study. p16 expression was found in 8 (16.3%) BL and 2 (20%) RLH cases. p27 was revealed in 29 (65.9%)BL and 9(90%) RLH cases, whereas 29(59.2%) BL and only 1 RLH expressed p53. Positivity for pRb2 was found in 42 (84.0%) of the BL and 8(80%)of the RLH cases. p21 and p14 were negative in all BL and RLH cases. In conclusion, our data indicate that heterogeneous RB (pRb2 or p16) and p53 (p53, p14, or p21) pathway alterations occur frequently in BL. Except for a much higher frequency of p53 protein expression in BL, close similarities were found between BL and RLH.