Understanding the mechanims responsible for cancer genome complexity has been an important goal for many decades. Umbreit et al. recently combined live cell imaging and single cell genome sequencing to analyze the cascade of genome rearrangements following the formation of a chromosome bridge in human cells (1). Their results suggest that this bridge leads to an initial breakage-fusion-bridge (BFB) cycle, followed by additional BFB cycles interwoven with episodes of micronucleation and chromothripsis, to generate complex genome rearrangements (1). This conclusion is strikingly consistent with the previously proposed “interphase breakage model” (2).