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Referring to any central nervous system (CNS) involvement with preceding or concurrent systemic disease, secondary CNS lymphoma (SCNSL) lacks a clear standard of care and historically carries a very poor prognosis. Aggressive histologies predominate, most notably diffuse large B cell lymphoma (DLBCL), with higher relative frequency in Burkitt lymphoma but lower absolute incidence. Therapeutic strategies commonly feature intensive CNS-penetrant chemotherapy, including methotrexate, cytarabine, and others. Combination regimens, novel targeted agents, and cellular therapy considerations are reviewed, noting that patients with SCNSL are often excluded from clinical trials and dedicated SCNSL studies are historically limited. Given these challenges, there has been renewed attention on CNS prophylaxis as well as strategies for early CNS detection. Prophylaxis is standard of care in Burkitt lymphoma, whereas its role in DLBCL and related histologies is increasingly unclear.