That our chromosomes can break and reshuffle pieces of themselves is nothing new; scientists have recognized this for decades, especially in cancer cells. The rules for where chromosomes are likely to break and how the broken pieces come together are only just now starting to come into view. Researchers have brought those rules into clearer focus by discovering that where each of the genome’s thousands of genes lie within the cell’s nucleus — essentially, the genome’s three-dimensional organization — holds great influence over where broken chromosome ends rejoin. This knowledge could shed light on fundamental processes related to cancer and normal cellular functions — for example, in immunity.