Diagnostic evaluation and treatment approach for patients with secondary CNS lymphoma. Secondary CNS involvement in aggressive lymphomas can be leptomeningeal or parenchymal, with symptoms related to disease location. Initial assessment includes neuroimaging and PET/CT associated with CSF evaluation (cytology and flow cytometry) and appropriate tissue biopsies. Testicular ultrasound is also required to complete the assessment for male patients. Treatment options comprise systemic immunochemotherapy with agents capable to cross the BBB and IT chemotherapy associated with ASCT, anti-CD19 CAR T-cell therapy, or BTKis, when appropriate.