Understanding the mechanisms that allow clonal hematopoietic stem cells (HSCs) to expand and cause disease will be critical for developing strategies to identify patients at high risk for adverse clinical outcomes who may benefit from pre-emptive interventions. A major limitation to such studies is the fact that clonal HSCs are often present at low frequencies and intermixed with their unmutated counterparts. Stephen Chung, MD, of the University of Texas Southwestern Medical Center discusses his team’s efforts to overcome this limitation by identifying cell surface markers present on clonal HSCs that will allow them to prospectively purify them for further functional and molecular studies.