Many transcription factors have been found to be oncogenic either when functionally altered through fusion with other proteins or through deregulated expression. However, still little is understood about the mechanism by which these proteins can transform cells of different origin. The Myb transcription factor is emblematic in this respect. Several forms of Myb can transform hematopoietic cells of different lineages in the chicken and Myb has been shown to be required for murine fetal hematopoiesis and to regulate the growth and differentiation of hematopoietic cells of several animal species. The role of the transcriptional activity of Myb and its possible gene targets in transformation are critically discussed.