Two major prognostic subtypes of CLL are defined by mutational status of variable region within the immunoglobulin heavy chain gene (IgVH) of the B-cell receptor (BCR); mutated (M) IgVH genes are associated with favourable outcomes, whereas cases harbouring unmutated (UM) IgVH genes, which can also express ζ-chain (T-cell receptor)-associated protein kinase of 70 kDa (ZAP-70) and CD38, display more aggressive disease and more frequently require therapeutic intervention [18,19]. This evidence concerns the gene BCR and B-cell chronic lymphocytic leukemia.