B-cell malignancy; most occur in immunosuppressed pts (organ transplantation, HIV). May present as a single mass lesion or as multiple mass lesions or meningeal disease. Dramatic, transient responses occur with glucocorticoids; therefore, whenever possible, steroids should be withheld until after biopsy has been obtained. Pts should be tested for HIV and the extent of disease assessed by performing positron emission tomography (PET) or CT of the body, MRI of the spine, CSF analysis, and slit-lamp examination of the eye. In immunocompetent pts, high-dose methotrexate produces median survival up to 50 months, which may be increased with concurrent whole-brain RT and combinations of other chemotherapeutic agents such as cytarabine or rituximab. In immunocompromised pts, prognosis is worse and treatment is with high-dose methotrexate, whole-brain RT, and, in HIV, antiretroviral therapy.