For diagnosis and monitoring of Sézary syndrome flow cytometric quantification of CD7- and CD26- T-cells is widely used. Because antigen loss is a characteristic but not disease-specific finding we investigated the significance of this approach. Therefore we analyzed the prevalence of tumor cells in FACS-sorted CD7+/- as well as CD26+/- circulating T-cells applying a clone-specific qualitative and quantitative T-cell receptor PCR. Tumor cells varied considerably in the CD7+ and CD7- cell subset but were largely confined to the CD26- population. We conclude that quantification of CD26- T-cells reflects the tumor cell amount more accurate and should be preferred in the clinical setting.