In a general surgical pathology practice, cases of acute myeloid leukemia (AML), including myeloid sarcoma, are relatively rare; the diagnosis is very often difficult, however, and consequences of a missed or improper diagnosis compromise patient care. Currently, accurate diagnosis of every case of AML requires integration of the morphological features and results of cytochemical and immunohistochemical stains, flow cytometric immunophenotyping, cytogenetics, and molecular studies. This review focuses on a practical approach to diagnosis of AML according to current standard of practice and discusses some of recent changes in the field of AML.