Based upon the observation by Pasqualucci et al. that NPMc+ immunohistochemical pattern may detect clonal multilineage involvement in NPM1-mutated AML [102] and that limited and inconclusive information had previously been reported on immunohistochemical examinations to investigate sub-cellular localization of NPM1 protein in non-acute MNs [12,40,49,69], we have hypothesized that in rare cases of either MDS or MDS/MPN with a blast count invariably <20%, but showing NPM1 mutation on molecular assays, AML may be under-diagnosed [69]. This evidence concerns the gene NPM1 and acute myeloid leukemia.