For equal segregation, chromosomes, which are distributed randomly in the nucleus of interphase, must be aligned at the spindle equator in mitosis before the onset of sister chromatid separation. The spindle checkpoint is a surveillance mechanism that delays the onset of sister chromatid separation while each chromosome is on the way to the spindle equator. Failure in the function of the checkpoint results in aneuploidy/polyploidy, which would be a cause of cancer. Here, we review chromosome dynamics in mitosis, molecular mechanisms of the spindle checkpoint and finally tumorigenesis triggered by missegregation of chromosomes.