Chromoanasynthesis is a distinct entity within the complex rearrangement phenomena grouped under the name chromoanagenesis. The formation of chromoanasynthesis is linked to defective or interrupted DNA replication, due to various replicative stress factors. Two alternative replication-based mechanisms (FoSTeS and MMBIR) can then act to induce a series of microhomology-dependent templates and switching events before the completion of DNA synthesis on the original template. These mechanisms lead to the formation of clusters of complex chromosome rearrangements, generally characterized by duplications and triplications. Chromoanasynthesis operates in the germline and during early embryonic development through the formation of micronuclei or chromatid bridges during mitotic divisions. The phenomenon has mainly been described in congenital diseases, but more recently cases of chromoanagenesis have been described in cancers.