Interest has recently reawakened in whether loss of the heterochromatic X 
chromosome (Barr body) is prevalent in certain breast and ovarian cancers, and 
new insights into the mechanisms involved have emerged. Mitotic segregation 
errors commonly explain the loss of the inactive X chromosome (Xi), but 
compromise of Xi heterochromatin in some cancers may signal broader deficits of 
nuclear heterochromatin. The debated link between BRCA1 and Xi might reflect a 
general relationship between BRCA1 and heterochromatin, which could connect 
BRCA1 to both epigenetic and genetic instability. We suggest that 
heterochromatic instability is a common but largely unexplored mechanism, 
leading to widespread genomic misregulation and the evolution of some cancers.