B-MYB belongs to the MYB family of transcription factors that include A-MYB and c-MYB. While A-MYB and c-MYB are tissue-specific, B-MYB is broadly expressed in rapidly dividing cells of developing or adult mammals. B-MYBs liaisons with important players of the cell cycle and transcription machinery, such as E2F and retinoblastoma proteins, suggest that its essential function in stem cell formation and mammalian development could be related to its ability to directly or indirectly impinge on gene expression. Besides its role in the cell cycle, B-MYB has been shown to promote cell survival by activating antiapoptotic genes such as ApoJ/clusterin and BCL2. Here, we discuss how B-MYB could be implicated in tumourigenesis by regulating gene expression.