Approximately 75% of AML cases exhibited aberrant marker expression within the CD34+CD38− compartment (e.g., CLL-1, lineage markers). Using this combined immunophenotypic and light-scatter–based approach, putative leukemic and normal stem cell populations could be distinguished in ∼47% of samples, with a median of 82% of the CD34+CD38− fraction identified as neoplastic, and higher LSC frequencies associated with inferior clinical outcomes. The gene discussed is CLEC12A; the disease is acute myeloid leukemia.