Acute myeloid leukemias (AMLs) with monocytic differentiation with or without recurring cytogenetic abnormalities have prognostic significance. Therefore, it is important to recognize such cases. Monocytic differentiation is identified by morphology and confirmed by cytochemical stains or flow cytometry. However, the materials for such analyses are not always available (air-dried aspirate smears, touch preparations, fresh cells). Thus, the utility of CD163, a hemoglobin scavenger molecule present on monocytes/macrophages, in identifying a monocytic component in AML in fixed, paraffin-embedded bone marrows was assessed. Using tissue microarrays, 31 cases of AML with monocytic differentiation and 35 cases without monocytic differentiation were evaluated in a blinded fashion for CD163 positivity and compared with CD68. Diagnoses were previously well established using cytochemistry and flow cytometry techniques. CD163 immunoreactivity was seen in 49% of AML cases with and 6% (2/35) without monocytic differentiation. CD68 was positive in 81% of AML cases with and 17% without monocytic differentiation. CD163 showed superior specificity for a monocytic component in AML compared with CD68 (94% vs. 83%). However, the suboptimal sensitivity (49%) limits its utility as a definitive marker of monocytic differentiation if negative in paraffin sections. These findings demonstrate that CD163 is helpful for the evaluation of a monocytic component in AML. When positive, correlation and evaluation for an associated recurring cytogenetic abnormality is warranted.