Most, if not all, malignancies have recurrent and disease-specific clonal chromosomal abnormalities, which play a pivotal role in tumor development. These comprise deletions or amplifications involving entire chromosomes or subchromosomal regions and, also, translocations. The latter represent the juxtaposition of fragments of DNA that are usually on different chromosomes. Most translocations are not random, involving, in a given disease, circumscribed regions of DNA within both chromosomal partners and are furthermore, reciprocal, with DNA being interchanged between both partners, implying that both chromosomal ends have to be brought into close apposition. Some chromosomal regions and localized areas within certain genes appear to be particularly prone to chromosomal aberrations, with specific abnormalities occurring within cells of a given lineage at specific stages of differentiation. 1 While some genes are involved in translocations involving only one partner gene, others are involved with multiple different partners. The MLL gene and, in particular, an 8.3-kilobase (kb) region (the breakpoint cluster region), is recurrently involved in a large number of different translocations, principally in acute myeloid leukemias. 2 The immunoglobulin (IG) loci show comparable promiscuity in their translocation partners, and recently many new translocations have been identified, using defined breaks within the IG loci to clone the translocation breakpoint. Table 1 lists the cloned translocations involving the IG loci; several other recurrent IG translocations remain to be cloned. 3-5 Here, we first review the IG translocations and, secondly, how the involved genes may contribute to the pathogenesis of B-cell malignancies.