During cell division in a mother cell, the 23 chromosomes that carry the human genome must be first copied and later delivered to two newly forming daughter cells. At least in healthy cells, the result is astonishingly flawless, and no chromosome is ever lost. Not so in malignant cells, where rampant chromosome segregation errors generate a continuous flux of new genetic variants that support metastatic growth and resistance to chemotherapy. A multilayered protein structure called the kinetochore executes the chromosome delivery program.