OBJECTIVE The receptor for stem cell factor (CD117) is the gene product of the c-kit proto-ontogene. Together with its ligand, the stem cell factor (SCF), it plays an important role in hematopoiesis. In this study, we review the cellular distribution of CD117 in normal hematopoiesis and in hematopoietic malignancies focusing on the differential expression in subtypes of acute leukemias. METHODS This review is based on a literature search in the Medline database, personal publications and results obtained as a reference laboratory of the German AML-BFM, AMLCG and ALL multi-center therapy studies. CONCLUSIONS Membrane expression of CD117 can be found on leukemic blasts from approximately 60% of adult and childhood AML patients, often associated with an immature immunophenotype (CD34). Moreover, AML with t(8;21) are frequently CD117 positive. Despite earlier reports, most recent studies have not been able to demonstrate any significant prognostic impact of CD117 expression in either childhood or adult AML. A small proportion of T-lineage ALL (9%), mainly consisting of immature pro-T/pre-T-ALL, is CD117 positive. CD117 expression is rare in B-cell-precursor-ALL and occurs in less than 3% of cases. CD117 in combination with other antigens might facilitate the immunologic characterization of acute leukemias, especially those of myeloid and early T-cell origin.