Summary: Human natural killer (NK) cells can be divided into two phenotypically distinct functional subsets based on their cell surface expression of CD56 (CD56bright and CD56dim). As mouse NK cells do not express CD56, comparable mouse NK cell subsets have proven difficult to identify. Recently, we have found that mouse NK cells can be subdivided by the expression of CD27. The CD27hi and CD27lo mouse NK cell subsets show some intriguing similarities to but also some distinct differences from the human CD56 NK cell subsets in terms of their function and phenotype. Extending our knowledge of mature NK cell heterogeneity between the species will be critical to further our understanding of the pathological role of NK cells in immune responses.