How do the various cancers arise and what factors determine their progression? Clues to these two issues, at least for leukemia, have now been provided by Boris Kovacic and colleagues at the University of Veterinary Medicine, Vienna. It is well known that many types of cancer arise as a result of a mutation in a cell, and prevailing wisdom has held that the stage of differentiation of this cell determines exactly what form of cancer develops. For example, it was believed that chronic myeloid leukemia (CML) arises from bone marrow stem cells, while a different type, known as B-cell acute lymphoid leukemia or B-ALL, results from B-cell precursors. The new research has shown that both CML and B-ALL arise from the most primordial kind of blood cell (long-term haematopoietic stem cells), although the pathways by which the diseases progress are different.