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Despite the identification of certain risk factors for non-Hodgkin's lymphoma (discussed in detail in the next section), most patients who develop non-Hodgkin's lymphoma (NHL) do not belong to any of these high-risk categories. Although major advances have been made in our understanding of the biology and physiology of cancers in general, currently, researchers still do not completely understand the basic scientific question of what causes a normal lymphocyte to become transformed into a cancerous lymphoma cell. What researchers do know with some degree of certainty is that mutations (alterations) in the DNA - the body's genetic code that regulates cellular function and controls the inheritance of characteristics - can speed up the rate of cell division through specific genes that can turn a normal cell into a cancer cell.

In addition to mutations in the DNA, scientists also believe that non-Hodgkin's lymphoma may be caused by a mechanism called DNA translocation. This occurs when DNA from one of the 23 pairs of chromosomes in a normal cell breaks off and "translocates" (moves) by attaching to a different chromosome. This new, abnormal chromosome is thought to trigger the sequence of cellular events that eventually lead to the development of non-Hodgkin's lymphoma.