Are there three different RUNX genes in the human genome just to allow differential expression in different cell types or are the RUNX proteins functionally different? Much previous evidence has suggested that the RUNX proteins were functionally redundant but, in human B cells, RUNX1 and RUNX3 have clearly been shown to have different functions at a key developmental stage. RUNX1 is expressed in mature resting B cells but proliferating B cell lines express RUNX3. Repression of RUNX1 by RUNX3 is required to allow the cell proliferation and this provides an experimental system to investigate the mechanism of the different activities of RUNX1 and RUNX3 in these cells.