We explored the nature of chromosome 13 loss in cultured human vascular endothelial cells (HUVECs). Chromosome 13 loss detected by metaphase and interphase analysis was noted in earlier passages of HUVEC strains with no relation to telomere length or replicative senescence. Ectopic expression of telomerase did not influence the loss of chromosome 13. HUVECs losing chromosome 13 demonstrated increased migratory potential and loss of heterozygosity. Collectively, these observations suggest that the loss of chromosome 13 gives cultured HUVECs a replicative advantage.