Enumeration of neoplastic T-cells in peripheral blood specimens is necessary for the diagnosis of Sézary syndrome (SS) and monitoring treatment responses. Because neoplastic T-cells in SS can be difficult to identify by morphology alone, flow cytometry immunophenotyping is often utilized. However, the reported immunophenotypic criteria for identifying neoplastic T-cells in SS are variable, not present in all cases, or sometimes found in reactive T-cell populations. Peripheral blood lymphocytes from 33 cases of SS were evaluated for the expression of pan-T cell antigens and killer cell immunoglobulin-like MHC receptors (KIR) CD158a, CD158b, CD158e, CD158i, and CD158k by multiparameter flow cytometry using monoclonal antibodies EB6, GL183, FES172, Z27, and Q66. A variety of abnormalities related to expression of pan-T-cell antigens typical of neoplastic T-cells were observed. Expression of CD158k was observed in 32/33 cases and restricted to the phenotypically abnormal T-cell populations, while expression of other KIR was mostly negative. Our findings confirm and extend recent reports by one group that CD158k is expressed by most SS cases. Moreover, our observation that CD4 positive, CD7 negative T-cells are mostly CD158k negative further suggests that CD158k may be able to help identify and enumerate neoplastic T-cells in SS even when present at low levels.