The exact cause of central nervous system (CNS) lymphoma is unknown, but a compromised immune system appears to be the greatest risk factor. Immune system deficiencies may be:

• Present at birth
  
• A side effect of chemotherapy
  
• Related to anti-rejection drugs for organ transplants
  
• Caused by HIV infection or AIDS
  
• Related to other conditions, such as Epstein-Barr virus (causes mononucleosis and is associated with Burkitt's lymphoma)

Certain inherited diseases also increase the risk of CNS lymphoma, including:

• Family history of lymphoma.
  
  
• Neurofibromatosis type 2. Inherited genetic disorder that causes brain tumors.
  
  
• Tuberous sclerosis. An inherited genetic disorder that causes benign tumors that affect the brain, eyes, skin and internal organs. It is also associated with mental retardation and seizures.
  
  
• Von Hippel-Lindau disease. Inherited genetic disorder that causes tumors of blood vessel cells that form in the retina, brain, spinal cord, pancreas, kidneys, and other organs.
  
  
• In addition, age (45 to 70), exposure to environmental toxins, obesity and radiation therapy may also be risk factors.