In summary, this case underlies on one side the biologic significance of the event ‘cytoplasmic positivity of NPM1′ as critical for leukemogenesis in AML, and on the other side the value of using several different techniques in routine diagnostics in order to recognize rare cases leading to similar alterations and define the strategy for MRD monitoring [17,21,32]. This evidence concerns the gene NPM1 and acute myeloid leukemia.