Chromosomal translocations that juxtapose antigen receptor genes and oncogenes are frequently associated with lymphoid malignancies. In this issue, Robbiani et al. (2008) show that activation-induced deaminase (AID), an enzyme involved in antigen receptor gene diversification, generates DNA double-strand breaks (DSBs) in oncogenes, and Tsai et al. (2008) propose that AID and the recombinase-activating gene (RAG) endonuclease may collaborate to generate off-target DSBs. © 2008 Elsevier Inc. All rights reserved.