Chromosomal elements control replication timing, condensation and stability. Mammalian chromosomes contain three types of cis-acting elements, origins of replication, centromeres, and telomeres, that function to maintain their proper number and structure. On pages 760–770 of this issue Mathew Thayer reviews recent discoveries that suggest that mammalian chromosomes contain a fourth type of element, referred to as ‘inactivation/stability centers’. Disruption of these ‘inactivation/stability centers’ leads to late replication, an under-condensed state during mitosis, and unattached kinetochores during metaphase (red). Fully condensed chromosomes are shown in green and mitotic spindles are shown in blue. These new observations suggest that mammalian chromosomes contain four distinct types of cis-acting elements that function to ensure proper replication, condensation, segregation and stability of individual chromosomes.