AbstractNatural killer (NK) cell tumors are an uncommon and heterogeneous group of disorders. The World Health Organization (WHO) classified mature NK cell neoplasms into 2 types: 1) extranodal NK cell lymphoma, nasal type and 2) aggressive NK cell leukemia. The mature NK cell tumors are prevalent in Asia and Central and South America. These tumors show polymorphic neoplastic infiltrate with angioinvasion and/or angiodestruction, cytoplasmic azurophilic granules, CD2‐positive (CD2+)/CD3‐negative (CD3−)/cCD3ε+/CD56+ phenotype, and strong association with Epstein‐Barr virus (EBV). Loss of chromosomes 6q, 11q, 13q, and 17p are recurrent aberrations. Although blastic NK cell lymphoma, currently referred to as CD4+/CD56+ hematodermic neoplasm, also was included in the NK cell lymphoma category in the WHO classification scheme, existing evidence indicates a plasmacytoid dendritic cell derivation as opposed to an NK cell origin. Recently, rare cases of CD56+ immature lymphoid tumors have been reported in the literature. These tumors are characterized by blastic appearance, CD3−/CD4−/CD56+/CD13−/CD33− phenotype, T‐cell receptor and immunoglobulin genes in germline configuration, and no evidence of EBV, suggesting a true immature NK cell derivation. For this article, the authors reviewed the recent concepts and progress in clinicopathologic features, pathogenesis, genetic characteristics, diagnosis, differential diagnosis, treatment approaches, and outcomes of all subtypes of NK cell neoplasms. Cancer 2008. © 2008 American Cancer Society.