NPM-immunostaining–based approach to molecular-cytogenetic study of AML. AML cases can be simply subdivided by immunohistochemistry in 2 groups (ie, expressing nucleus-restricted NPM [NPMc^–] or cytoplasmic NPM [NPMc⁺]; both figures were captured with an Olympus 100×/1.3 UPlanFl oil objective). The arrow in the NPMc^– panel indicates the expected cytoplasmic positivity of a mitotic figure. Molecular studies for recurrent genetic abnormalities can be avoided in NPMc⁺ AML since the 2 events are mutually exclusive. For the same reason, mutational analysis of NPM is unnecessary in patients with NPMc^– AML. Cytogenetics and other molecular studies should be performed in both NPMc⁺ and NPMc^– patients with AML for diagnostic and investigational purposes.