Nucleophosmin (NPM1) is a protein of highly conserved nature which works as a molecular chaperone and is mostly found in nucleoli. NPM also involved in the maturation of preribosomes and duplication of centrosomes. Furthermore, it is also active in control and regulation of the ARF-p53 tumor suppressor pathway. A high rate of incidence and prognostic involvement is reported by various authors in AML patients. In AML it behaves as a favorable prognostic marker. NPM mutations are more frequently associated with normal-karyotype AML and are usually absent in patients having abnormal or poor cytogenetic. NPM mutations are not frequent in other hematopoietic tumors. Two main types of mutations have been described to date. Both of these cause abnormal cytoplasmic localization of NPM1. Their high incidence rate in normal karyoptype and their favorable nature m ake those mutations hot spot or front face mutations which should be checked before treatment starts.