Background:Current diagnostic criteria for mature B-cell tumors require a combination of histopathological, immunophenotypic, cytogenetic, and genetic evaluations on tissue biopsy specimens (Campo, Blood2022; Alaggio, Leuk2022). Despite this battery of techniques, substantial heterogeneity remains in specific subgroups that can be further resolved using additional molecular diagnostic methods, including gene expression profiling (GEP). For example, among aggressive B-cell tumors, a subset recognized as high-grade B-cell lymphomas can be identified as harboring MYC+BCL2 lesions by FISH (HGBCL-DH-BCL2). However, a significant remaining high-risk subset also have a characteristic tumor gene expression “double-hit signature” or “dark zone signature” (DZsig) (Ennishi, JCO2018; Alduaij, Blood2023).