The promise of stem-cell therapy is long-term repair of damaged organs by transplantation. Inoculum size might be a determinant of successful repair, and efforts are being made to improve conditions for ex vivo expansion of stem cells prior to transplantation. A recent article by Damelin and colleagues raised concerns about this approach, demonstrating that stem cells lack the decatenation G2 checkpoint that preserves genetic stability. Cells that fail to disentangle chromatids prior to mitosis are prone to the types of chromosomal aberrations that are observed in cancer cells. Ex vivo expansion of stem cells might have the unintended consequence of encouraging malignant progression.