A hallmark of mature B-cell lymphomas is reciprocal chromosomal translocations involving the Ig locus and a proto-oncogene, which usually result in the deregulated, constitutive expression of the translocated gene. In addition to such translocations, proto-oncogenes are frequently hypermutated in germinal center (GC)-derived B-cell lymphomas. Although aberrant, mistargeted class switch recombination (CSR) and somatic hypermutation (SHM) events have long been suspected of causing chromosomal translocations and mutations in oncogenes, and thus of playing a critical role in the pathogenesis of most B-cell lymphomas, the molecular basis for such deregulation of CSR and SHM is only beginning to be elucidated by recent genetic approaches. The tumorigenic ability of activation-induced cytidine deaminase (AID), a key enzyme that initiates CSR and SHM, was revealed in studies on AID transgenic mice. In addition, experiments with AID-deficient mice clearly showed that AID is required not only for the c-myc/IgH translocation but also for the malignant progression of translocation-bearing lymphoma precursor cells, probably by introducing additional genetic hits. Normally, AID expression is only transiently and specifically induced in activated B cells in GCs. However, recent studies indicate that AID can be induced directly in B cells outside the GCs by various pathogens, including transforming viruses associated with human malignancies. Indeed, AID expression is not restricted to GC-derived B-cell lymphomas, but is also found in other types of B-cell lymphoma and even in nonlymphoid tumors, suggesting that ectopically expressed AID is involved in tumorigenesis and disease progression in a wide variety of cell types.