CD33 (gp67, or siglec-3) is a 67 kDa glycosylated transmembrane protein that is a member of the sialic acid-binding immunoglobulin-like lectin (siglec) family. CD33 plays a role in cell-cell interactions, signaling, and modulation of immune cell function. The CD33 antibody may be particularly advantageous for cases of acute myeloid leukemia, minimally differentiated (AML-M0) and acute monocytic leukemia (AML-M5), in which other paraffin section markers of myeloid differentiation (such as anti-myeloperoxidase) may be negative. All cases of myeloid sarcoma in this study showed anti-CD33 positivity in the myeloid and monocytic subsets, allowing for easy interpretation. The excellent sensitivity and specificity for myelomonocytic lineage makes this anti-CD33 a useful diagnostic marker for myeloid sarcoma. In addition, this anti-CD33 may be useful in determining CD33 expression on previous paraffin-embedded material if flow cytometry studies were not initially performed in patients with acute leukemia. Analysis of CD33 expression in paraffin-embedded bone marrow biopsy specimens provides another alternative when evaluating acute leukemias.