In this large-scale prospective study evaluating 6,412 circulating proteins in 4,565 EPIC participants, we identified key proteomic markers linked to early lymphoid malignancy pathogenesis (e.g. sBCMA, CXCL13, sCD23, CD28, CD72, FCRL1, FCRL3, SEMA4A, and SEMA7A) and reveal several promising novel protein markers associated specifically with germinal center-derived B-cell lymphoma (e.g. FDCSP, CCL21, CD40LG and SERPINA9) and non-germinal center-derived B-cell lymphoma subtypes (e.g. FCMR and SELL). This evidence concerns the gene CD28 and B-cell non-Hodgkin lymphoma.