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The three mammalian Runx genes encode transcription factors that play essential but distinct and lineage-specific roles in development. These sequence-specific DNA binding proteins share a common binding cofactor (CBFβ) that confers protein stability and high affinity for target DNA on its RUNX partners. An important link to cancer was first realised through identification of both RUNX1 and CBFB as frequent targets for chromosomal translocations in human leukaemia. Early studies suggested that RUNX1 is a tumour suppressor subject to dominant negative inhibition by its fusion oncoprotein derivatives and to loss-of-function mutations in AML (reviewed in [1]). However, it is now clear that RUNX1 is far from a typical tumour suppressor as, for example, AML cells expressing the RUNX1-ETO fusion require the activity of the unaffected allele for survival [2] while ALL cases frequently over-express RUNX1 and/or display increased copy number [1]. Moreover, early studies on mouse models of lymphoma revealed all three Runx genes as targets for transcriptional activation in MYC transgenic mice, and the ability of over-expressed MYC and Runx to synergise in lymphoma has been amply confirmed in compound transgenics [1].