Our current study revealed that HGBCL, NOS expressing DLBCL‐like signatures have higher genomic aberrations and are characterized by deletion of well‐characterized TSGs (e.g., PRDM1, CDKN2A, TP53, RB1), and recurrent mutations in MYD88 and PIM1 and may be therapeutically vulnerable to BCR and/or PIM1 inhibition as rational therapeutic approach. The gene discussed is MYD88; the disease is diffuse large B-cell lymphoma.