The World Health Organization (WHO) recognizes two histological groups, differentiating distinct clinico-pathological entities [2]: (I) classic HL (cHL), characterized by HRS cells (expressing surface CD30), dispersed throughout a heterogenous inflammatory infiltrate, and constituting more than 90% of cHL cases; (II) nodular lymphocyte-predominant HL (NLPHL), in which malignant cells are aberrant CD20+ lymphocytes (lymphocyte predominant (LP) cells) lacking typical HRS features (CD15- and CD30-), representing about 5–10% of HL cases. This evidence concerns the gene TNFRSF8 and Hodgkins lymphoma.