Polycomb group (PcG) proteins are transcriptional repressors with critical roles in preserving cellular identity and maintaining the pluripotency of embryonic stem cells. Dysregulation of PcG proteins has been observed in many aggressive subtypes of cancer. In their report, Yu and colleagues performed genome-wide location analysis of Polycomb in metastatic prostate cancer tissues. They identified a “Polycomb repression signature” in metastatic cancer that highly overlaps with PcG target genes in human embryonic stem cells. Repression of this signature predicts poor clinical outcome in multiple solid tumors across microarray datasets. These findings suggest a unifying role of PcG proteins in regulating embryonic stem cells, metastasis, and cancer survival. For details, see the article by Yu and colleagues on page 10657 of this issue.