Sézary syndrome and Mycosis fungoides are the most common forms of cutaneous T‐cell lymphomas. To assess the response to different therapies especially in Sézary syndrome, it is helpful to monitor the percentage of circulating tumour cells in the blood. The use of T‐cell receptor (TCR)‐Vβ specific monoclonal antibodies provides a suitable tool for detecting Sézary cells. In this study, we analysed the levels of clonal CD4⁺Vβ⁺ cells of seven patients with various treatment modalities using flow cytometry and investigated the immunophenotype of the clonal cells by double staining with a panel of antibodies recognizing lymphatic surface markers. Additionally, a polymerase chain reaction‐denaturing gradient gel electrophoresis assay was performed on clonal CD4⁺Vβ2⁺ cells, showing that these cells carry a Vγ10/11, JγP1/2 TCR rearrangement. Follow‐up studies revealed close association of the Vβ⁺ clone developmentwith the clinical response to different therapiesinsixpatients. Intwo cases, the CD4⁺Vβ⁺ cells decreased accompanied by partial regression or even complete remission. In four cases, a stable or increasing clonal CD4⁺Vβ⁺ population reflected well a stable or progressing course of the disease. Double staining of Vβ⁺ cells revealed the following pattern, CD3⁺, CD5⁺, CD7⁺, CD28⁺, CD80^–, CD86⁺ and human leucocyte antigen (HLA) class I⁺. In contrast, HLA‐DR was heterogeneously expressed. We conclude that identification and monitoring of CD4⁺Vβ⁺ clonal T cells by fluorescence‐activated cell sorting with double staining is a suitable method to assess clinical responses to different therapies.