Dicentric chromosomes are products of genomic rearrangements that place two 
centromeres on the same chromosome. Due to the presence of two primary 
constrictions, they are inherently unstable and overcome their instability by 
epigenetically inactivating and/or deleting one of the two centromeres, thus 
resulting in functionally monocentric chromosomes that segregate normally during 
cell division. Our understanding to date of dicentric chromosome formation, 
behavior and fate has been largely inferred from observational studies in plants 
and humans as well as artificially produced de novo dicentrics in yeast and in 
human cells. We investigate the most recent product of a chromosome fusion event 
fixed in the human lineage, human chromosome 2, whose stability was acquired by 
the suppression of one centromere, resulting in a unique difference in 
chromosome number between humans (46 chromosomes) and our most closely related 
ape relatives (48 chromosomes). Using molecular cytogenetics, sequencing, and 
comparative sequence data, we deeply characterize the relicts of the chromosome 
2q ancestral centromere and its flanking regions, gaining insight into the 
ancestral organization that can be easily broadened to all acrocentric 
chromosome centromeres. Moreover, our analyses offered the opportunity to trace 
the evolutionary history of rDNA and satellite III sequences among great apes, 
thus suggesting a new hypothesis for the preferential inactivation of some human 
centromeres, including IIq. Our results suggest two possible centromere 
inactivation models to explain the evolutionarily stabilization of human 
chromosome 2 over the last 5-6 million years. Our results strongly favor 
centromere excision through a one-step process.