Chromoplexy is a massive and complex rearrangement mechanism, occurring during a single cell event and characterized by the formation of chain rearrangements affecting multiple chromosomes. This can lead to the formation of fusion genes and the simultaneous disruption of several genes. Chromoplexy was first identified in prostate cancers, but it is now being observed in various cancers where gene fusions take place. The mechanisms underlying chromoplexy formation are still unclear. The occurrence of these rearrangements follows multiple double-stranded breaks that appear to occur in particular genome configurations (open chromatin, active transcription area, etc.) and which lead to intricate series of inter- and intra-chromosomal translocations and deletions without significant alterations in the number of copies. Although chromoplexy is considered a very early event in oncogenesis, the phenomenon can be repeated and constitute a mechanism of clonal tumor progression. The occurrence of chromoplexy supports the equilibrium model punctuated by tumor evolution, characterized by periods of relative stability punctuated by sudden and rapid periods of radical genomic changes.