Chromoanagenesis defines a group of highly complex chromosome rearrangements restricted to a single or few chromosomes that are suggested to occur in a single catastrophic event. Several experimental findings have connected chromoanagenesis to the formation of micronuclei, small extranuclear chromatin structures harboring a missegregated chromosome or a chromosome fragment. Experimental evidence points to the intrinsic fragility of the envelope around micronuclei as cause of membrane rupture. Consequently, the micronuclear DNA is exposed to various cytoplasmic activities producing the pattern of localized multiple breaks characteristic of chromoanagenesis. Here, we discuss results from combined microscopic and genomic approaches that directly connect micronucleus fate with chromoanagenesis. The major methods of investigation that allowed to identify the origin of chromoanagenesis from micronuclei are also presented.