Lymphoma. Lymphoma is a variety of cancer that originates in lymphocytes or, more rarely, of histiocytes. Collectively, these cell types form the reticuloendothelial system and circulate in the vessels of the lymphatic system. Just as there are many types of lymphocytes, so there are many types of lymphoma.Lymphoma is a group of blood cancers that develop from lymphocytes (a type of white blood cell). The name often refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph nodes, fever, drenching sweats, unintended weight loss, itching, and constantly feeling tired. What causes lymphoma to develop Lymphoma can develop when lymphocytes (white blood cells that fight infection) grow out of control. This is caused by genetic changes in the cells that mean they no longer 'listen' to signals that control their growth and death. Lymphomas are a heterogeneous group of malignancies that arise from lymphocytes. Since the first report of lymphoma by Thomas Hodgkin in, lymphomas have been grouped into either Hodgkin’s lymphoma or non-Hodgkin’s lymphoma (NHL). There were 601,180 patients with lymphoma (Hodgkin’s lymphoma and NHL) in the United States alone. Advances in technology have revealed multiple additional subtypes of NHL. Of these subtypes, diffuse large B-cell lymphoma (DLBCL) accounts for the largest percentage at of cases, and in the United States alone there are new diagnoses per year. Lymphomas are generally treatable with chemotherapy. Even so, the majority of patients with DLBCL and a number of other lymphoma subtypes will eventually succumb to their disease. This chapter will begin with an overview of lymphoma and discuss the influence of genomics on diagnosis, prognosis, and treatment, with emphasis on DLBCL, mantle-cell lymphoma, Burkitt’s lymphoma, and Hodgkin’s lymphoma. Lymphomas encompass a diverse, yet related, group of hematological neoplasms arising from B and T lymphocytes. They include non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), plasma cell neoplasms, and lymphoid leukemias, and collectively represent the sixth-most common malignancy in the United States. Their etiology is largely unknown, with immunodeficiency and specific infections being the only established risk factors. Epidemiological data show differences in temporal and demographic incidence patterns between lymphoma subtypes, which, together with observations from analytical studies, suggest differences in etiology. However, the diversity of lymphoma subtypes, together with difficulties surrounding disease classification, has greatly complicated the elucidation of clear etiologic determinants.Subtype-specific analyses have been hindered by the existence of classification schemes that have evolved over time. These schemes include the Working Formulation, the Revised European-American Lymphoma (REAL) classification , and the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (2001, 2008). The WHO Classification represents consensus classification for clinical, pathological, and scientific use and wholly incorporates the International Classification of Diseases for Oncology, Third Edition (ICD-O-3, 2001). The InterLymph nested hierarchical classification, a widely adopted epidemiological classification based on the 2008 WHO Classification, was proposed as a means of achieving homogeneity among cases diagnosed under different classification schemes within and between studies .