In normal human peripheral blood, cutaneous lymphocyte antigen is expressed by memory T cells, suggesting a specific tissue-homing population of T cells. In this study it is demonstrated that 6% of CD56 + natural killer cells in peripheral blood also express cutaneous lymphocyte antigen (CLA). It was also detected that most of the tumor cells in primary cutaneous nasal-type natural killer cell lymphomas were CLA-positive, whereas primary nasal natural killer cell lymphomas were CLA-negative. Although natural killer cells traditionally are known to be non-specific immune cells without antigen specificity and little is known about the role of natural killer cells in skin diseases, the results of this study suggest the existence of a subset of skin-associated CLA+ CD56+ natural killer cells. These natural killer cells may be related to the pathogenesis of primary cutaneous natural killer cell lymphomas.