A fragile site on the X chromosome is associated with a common form of mental retardation in males and a proportion of females.1-3 This association was not fully appreciated when the fragile site on the X was first described in 1969,4 but it is crystal-clear today. Chromosome fragility can be random, as in Fanconi anemia, Bloom syndrome, and ataxia-telangiectasia, the chromosome instability syndromes.5 Breaks and rearrangements of chromosomes are seen in these disorders, all of which are autosomal recessive conditions predisposing to cancer. Fragile sites are special spots in the genome where gaps and breaks occur nonrandomly. The balance of the chromosome complement is normal.