An in-depth study of SHM mechanism in CLL resulted in the classification of patients in two distinct subgroups based on the SHM imprint within both the rearranged immunoglobulin heavy variable (IGHV) gene and immunoglobulin kappa/lambda variable gene (IGKV/IGLV) of the clonotypic BcR IG. The gene discussed is BCR; the disease is B-cell chronic lymphocytic leukemia.