Here, we aimed to compare the anti-tumorigenic effect of a simultaneous SYK inhibition by Entospletinib with pan-BET inhibition by I-BET151 (I-BET) or isoform-specific bivalent BET inhibition by AZD5153 (AZD) in a DLBCL and Burkitt’s lymphoma in vitro approach. The gene discussed is SYK; the disease is diffuse large B-cell lymphoma.