The combined results from our patient cohort and xenotransplantation models indicate that active IL‐6R/STAT3 signaling is a negative prognostic factor and therapeutic target in DLBCL; biomarkers that may be useful in predicting therapy success include the expression of IL‐6R, gp130, and phospho‐STAT3. This evidence concerns the gene STAT3 and diffuse large B-cell lymphoma.