The transcription factor MYB has a key role as a regulator of stem and progenitor cells in the bone marrow, colonic crypts and a neurogenic region of the adult brain. It is in these compartments that a deficit in MYB activity leads to severe or lethal phenotypes. As was predicted from its leukaemogenicity in several animal species, MYB has now been identified as an oncogene that is involved in some human leukaemias. Moreover, recent evidence has strengthened the case that MYB is activated in colon and breast cancer: a block to MYB expression is overcome by mutation of the regulatory machinery in the former disease and by oestrogen receptor-α (ERα) in the latter.