Members of Polycomb Repressive Complex 2 (PRC2) including SUZ12, EED, and EZH2 catalyze the formation of a di- or trimethyl mark on lysine 27 of Histone H3 (H3K27) through their interaction. The methyltransferase EZH2 behaves as a context-dependent oncogene or tumour suppressor in multiple human cancers and its overexpression is associated with poor prognosis in human breast cancer. This is related to the important role of PRC2 in instructing cell differentiation through transcriptional silencing. We have previously shown that deletion of EZH2 in the mouse mammary epithelium delays mammary gland outgrowth and impairs alveologenesis during pregnancy, but does not lead to overt defects in cell differentiation (1, 2). Consistent with a partially redundant role for EZH2 in the mammary gland, it has been suggested that a second methyltransferase, EZH1, may compensate for EZH2’s function. We now show that disruption of PRC2 through deletion of SUZ12 results in the complete absence of a mammary gland, indicating it has a non-redundant role in mammary stem and progenitor cells. Unexpectedly however, we find that deletion of SUZ12 results in increased metastatic potential of a breast cancer cell line. We are currently investigating this to understand the implications of targeting the PRC2 complex in breast cancer.