Whereas the mutational patterns of cancers related to specific carcinogens are known, the mutational spectra of many other cancers are not well understood. Now, Michael Stratton and colleagues report the sequencing of 21 breast cancer genomes and a sophisticated analysis investigating the mutational forces shaping these cancer genomes (Cell 149, 979–993, 2012). After cataloging somatic mutations, the authors considered the nucleotide context in which the mutations occurred. By systematically looking at the nucleotides both 5′ and 3′ to the mutated base pair, the authors found an overrepresentation of C>T substitutions at XpCpG trinucleotides. The authors attribute these mutations to the deamination of methylated cytosine to thymine. Other mutational contexts were overrepresented, although the underlying mechanisms are not known. The authors employed a mathematical approach called nonnegative matrix factorization (NMF) and modeled selection to extract mutational signatures from the 21 cancers, finding evidence for five biologically distinctive mutational signatures. They also calculated intermutational distances and observed regional hypermutation in some cancers, a phenomenon they call 'kataegis' (Greek for shower or thunderstorm). These mutations were present in cis, such that they occurred on the same DNA strand, perhaps simultaneously or in a sequential manner over a short time period.