Multicolor flow cytometry (MFC), combined with molecular and cytogenetic studies, is the most common method for detecting minimal residual disease (MRD) in acute myeloid leukemia (AML). Studies have shown that a positive MFC MRD study after induction and/or consolidation, or before allogeneic hematopoietic stem cell transplantation, correlates with risk of relapse and inferior survival. However, there is little information on technical and analytical details. This article shares the authors' experience using MFC for AML MRD detection, including antibody panel design, data analysis, and interpretation. It summarizes diagnostic pearls and pitfalls, and provides practical information for pathologists or hematologists.