A few changes have been introduced in the fourth edition of the WHO classification regarding DLBCL [2]: (1) the “cell of origin” (COO) classification must be included in the pathology report; (2) CD5, MYC, and BCL2 immunohistochemical expression must be assessed as prognostic factors; (3) the provisional entity “B cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma” has been replaced by two new categories: “high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 translocations” and “high-grade B-cell lymphoma, not otherwise specified”. This evidence concerns the gene MYC and diffuse large B-cell lymphoma.