Increased expression of the protein methyltransferase Ezh2 turns hematopoietic stem cells into leukemic stem cells, causing the development of bone marrow related myeloproliferative disease. These findings, reported in a paper published in Nature Communications this week, may aid the development of new drugs to treat cancers of the blood. The role of Ezh2 in cancer has been controversial, with recent studies suggesting that it can act both as an oncogene and tumour suppressor. Susana Gonzalez and colleagues forced the expression of Ezh2 specifically in the hematopoietic stem cells of mice and observed that they developed fatal myeloproliferative disease, characterized by an excessive expansion of myeloid cells in the bone marrow and leading to an abnormally enlarged spleen. In addition, they show that the disease originates in hematopoietic stem cells, since Ezh2 expression causes an increase in the levels of stem cell-specific genes, known to be abnormally expressed in hematological tumours. The authors conclude that Ezh2 has a stem cell-specific role as an oncogene in myeloid disorders, suggesting that it can potentially be targeted for their treatment.