Outline for the workup and management of aggressive B-cell lymphomas. Typically, morphological, immunohistochemistry, and FISH analysis are performed to differentiate DLBCL from HGBL. HGBL cases are divided into those that are DHL/THL or NOS. For DLBCL cases that have a high-protein expression of MYC and BCL2, which are usually of ABC origin, dose-intensive therapy or enrollment in a clinical trial should be considered, particularly for patients with a high IPI score.