The activation-induced cytidine deaminase (AID) targets DNA mutations and breaks to immunoglobulin loci in B cells during the processes of somatic hypermutation and class switch recombination, but aberrant targeting of non-immunoglobulin loci can lead to oncogenic mutations. Now, James Bradner, Frederick Alt and colleagues (Cell 159, 1538–1548, 2014) and Marei Dose, Rafael Casellas and colleagues (Cell 159, 1524–1537, 2014) report new insights into the causes of mistargeting by AID. Bradner, Alt and colleagues mapped AID off-target sites in mouse B cells by using high-throughput genome-wide translocation sequencing to identify double-strand break hotspots and characterized the B cell transcriptome using global run-on sequencing. They found that AID targets are characterized by overlapping sense and antisense transcription, termed convergent transcription, at intragenic enhancers with high levels of acetylation at lysine 27 of histone H3 (H3K27ac). Dose, Casellas and colleagues mapped AID targets across the genome in mouse B cells, using replication protein A chromatin immunoprecipitation, and in human B cells and B cell tumors, using deep sequencing. They found that AID preferentially targets promoters and enhancers tethered by long-range interactions and transcribed enhancers with high chromatin accessibility. These concordant studies provide new insights into the genomic determinants of AID off-target mutagenic activity.