The original definition of NK cells was based on their ‘natural’ cytolytic response against tumor cells and virus-infected cells in the absence of specific immunization. However, the term ‘natural killer’ reflects neither the education/maturation requirements before NK cells can kill nor the entirety of their biological functions. In light of new functional assays, genetic models and genomics analysis, we propose a more accurate definition of NK cells. This definition includes the phenotypical identification of NK cells as CD3⁻NKp46⁺ cells across mammalian species. In general, this attempt to redefine NK cells also highlights the need to update the operational definition of cell types in the post-genomic area.