Prior to analysis of the IGHV gene mutational status and based on immunophenotypic analysis, CLL B-cells were thought to be derived from malignant transformation of follicular mantle-zone B-cells, which normally expresses CD5, CD23, coexpress membrane IgM and IgD, are negative for CD38 and use unmutated Ig V region genes (157). This evidence concerns the gene FCER2 and B-cell chronic lymphocytic leukemia.