Burkitt's lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, the Irish surgeon who first described the disease in 1958 while working in equatorial Africa. It is a highly aggressive form of cancer which often, but not always, manifests after a person develops acquired immunodeficiency from infection with Epstein-Barr Virus or Human Immunodeficiency Virus (HIV).

The overall cure rate for Burkitt's lymphoma in developed countries is about 90%. Burkitt's lymphoma is uncommon in adults, in whom it has a worse prognosis.

Burkitt lymphoma can be divided into three main clinical variants: the endemic, the sporadic, and the immunodeficiency-associated variants. By morphology (i.e., microscopic appearance), immunophenotype, and genetics, the variants of Burkitt lymphoma are alike.

Burkitt lymphoma is commonly associated with the infection of B cell lymphocytes with the EBV and in these cases is considered to be one form of the Epstein–Barr virus-associated lymphoproliferative diseases. The endemic variant of Burkitt lymphoma is in almost all cases associated with EBV infection. The fact that some Burkitt lymphoma cases do not involve EBV allows that many cases of the disease are not caused and/or promoted by EBV, i.e. the virus may be an innocent passenger virus in these cases. However, the almost ubiquitous presence of the virus in the endemic variant of Burkitt lymphoma suggests that it contributes to the development and/or progression of this variant. The mutational landscape in Burkitt lymphoma has recently been found to differ between tumors with and without EBV infection, further strengthening the role of the virus in disease origin.

Almost all cases of Burkitt lymphoma are characterized by dysregulation of the c-myc gene by one of three chromosomal translocations which place the myc gene under the control of an immunoglobulin gene enhancer. The MYC gene is found at 8q24.

The c-myc gene found on chromosome 8 is part of the MYC family of genes that serve as regulators of cellular transcription and is associated with Burkitt lymphoma. Expression of the c-myc gene results in the synthesis of transcriptional factors that increase the expression of other genes involved in aerobic glycolysis. Ultimately, an increase in aerobic glycolysis plays a role in providing the necessary energy for cellular growth to occur. The translocation of the c-myc gene to the IGH, IGK, or IGL region moves the gene to a location in the genome near immunoglobulin enhancers which increases the expression of the c-myc gene. Overall, this translocation leads to increased cellular proliferation that is found in Burkitt lymphoma. Point mutations can also be present in the translocated c-myc gene resulting in the expressed c-myc protein being overactive.

Bcl-2 translocations, which are frequently seen in follicular lymphomas and other B-cell Non-Hodgkin Lymphomas, do not occur in Burkitt lymphomas.

One of the above described translocations of MYC is seen in 90% of cases of Burkitt lymphoma, but these oncogenic translocations are not usually sufficient to cause lymphoma; other mutations must also be present. These additional mutations include mutations of the tumor suppressor TP53, which interacts with the tumor suppressor p53 (which usually causes apoptosis in B cells carrying the disordered MYC oncoprotein). But with TP53 and p53 mutated, apoptosis is blocked, and the oncogenic B-cells are allowed to proliferate unchecked. The tumor suppressors ARF and USP7 are also frequently mutated in Burkitt lymphoma leading to MDM2 inhibition of the tumor suppressor p53 which then leads to enhanced oncogenesis. SIN3A, a regulator of MYC, that acts to inhibit MYC by deacetylating it, is often inactivated in Burkitt lymphoma. Also, sequential mutations of the RNA helicases (involved in RNA synthesis) DDX3X (found on the x chromosome) and DDX3Y (found on the y chromosome) lead to MYC oncogenesis in Burkitt lymphoma. Early in the pathogenesis process, DDX3X mutations limit translation (protein synthesis) allowing lymphoma cells to escape MYC induced proteotoxic stress and apoptosis, then later, DDX3Y mutations restore high level protein synthesis (by producing the translational machinery) and leading to increased proliferation of tumor cells. These sequential DDX3X and DDX3Y mutations are thought to partially explain why Burkitt lymphoma is more common in males as the DDX3Y RNA helicase is only found on the Y chromosome.