Human chromosome 9 is involved in a number of recurrent structural rearrangements; moreover, its pericentromeric region exhibits a remarkable evolutionary plasticity. In this study we present the molecular characterization of a constitutional rearrangement, involving the 9p21.1q13 region, which led to the formation of a supernumerary marker chromosome (SMC). We defined the sequence of the breakpoints and identified a new set of duplicons on human chromosome 9, named LCR9s (chromosome 9 low-copy repeats). Two of these duplicons were shown to be involved in a somatic exchange leading to the formation of the SMC. High-resolution FISH coupled to database search demonstrated that a total number of 35 LCR9 paralogs are present in the human genome. These newly described chromosome 9 duplicons have features that may be crucial in driving structural chromosome rearrangements in germinal and somatic cells.