Updated project metadata. The aggressive B cell lymphoma diffuse large B cell lymphoma (DLBCL) is a heterogeneous entity that requires more precise monitoring and prognosis molecular tools. Extracellular vesicles that are secreted by all cell types are currently recognized as serving as a proxy for the cell of origin. Utilizing cutting-edge mass spectrometry, the current study described and assessed the plasma small extracellular vesicles (sEVs) proteome's diagnostic and prognostic potential. The presence of DLBCL has a significant impact on the sEV proteome, and several proteins substantially correlate with DLBCL.Nevertheless, no proteins that highly correlated with non-GCB or GCB were found.