CD33 (Siglec-3) is expressed on most acute myeloid leukemia (AML) cells and is currently being exploited as a therapeutic target. The purpose of this study was to investigate the expression pattern and potential utility of the seven recently described CD33-related siglecs as markers in AML. Besides CD33, Siglec-9 was the most highly expressed, particularly on AML cells with features of monocytic differentiation that also expressed Siglecs-5 and -7. Siglec-9 was absent from normal bone marrow myeloid progenitors but present on monocytic precursors. Using primary AML cells or transfected rat basophilic leukemia cells, Siglec-9 mediated rapid endocytosis of anti-Siglec-9 mAb. In contrast to CD33 and Siglec-5, levels of soluble Siglec-9 were low or undetectable in bone marrow plasma from AML patients and serum from normal donors. These features suggest that Siglec-9 provides not only a useful marker for certain subsets of AML, but also a potential therapeutic target.