Acute monocytic leukemia (AMoL, or AML-M5) is considered a type of acute myeloid leukemia. In order to fulfill World Health Organization (WHO) criteria for AML-5, a patient must have greater than 20% blasts in the bone marrow, and of these, greater than 80% must be of the monocytic lineage. A further subclassification (M5a versus M5b) is made depending on whether the monocytic cells are predominantly monoblasts (>80%) (acute monoblastic leukemia) or a mixture of monoblasts and promonocytes (<80% blasts). Monoblasts can be distinguished by having a roughly circular nucleus, delicate lacy chromatin, and abundant, often basophilic cytoplasm. These cells may also have pseudopods. By contrast, promonocytes have a more convoluted nucleus, and their cytoplasm may contain metachromatic granules. Monoblasts are typically MPO negative and promonocytes are MPO variable. Both monoblasts and promonocytes stain positive for non-specific esterase (NSE), however NSE may often be negative.

Immunophenotypically, M5-AML variably express myeloid (CD13, CD33) and monocytic (CD11b, CD11c) markers. Cells may aberrantly express B cels marker CD20 and the NK marker CD56. Monoblasts may be positive for CD34.
M5 is associated with characteristic chromosomal abnormalities, often involving 11q23 or t(9;11)affecting the MLL locus, however the MLL translocation is also found in other AML subtypes. MLL is believed to be prognostically unfavorable in AML-M5 compared to other genetic alterations involving MLL such as t(9;11) The t(8;16) translocation in MLL is associated with hemophagocytosis.

AML-M5 is thought to be associated with exposure to epidophyllotoxins.
AML-M5 is treated with intensive chemotherapy (such as anthracyclines) or with bone marrow transplantation.