Flow cytometry has a well-established role in the detection of peripheral blood involvement by Cutaneous T-cell Lymphoma (CTCL) / Sezary syndrome (SS). Recognition of the characteristic CD4(+), CD7(-), CD26(-) T-cell immunophenotype led to early incorporation of flow cytometric parameters into diagnostic criteria for overt disease, such as CD4:CD8 ratio, and proportion of CD4(+), CD7(-) and CD4(+), CD26(-) T-cells. However, a recent multi-institutional survey demonstrated significant variability in the assays offered by different laboratories and the information included in flow cytometric reports. Therefore, an international group of cytometrists was convened to establish guidelines for the harmonization of flow cytometric assays for CTCL / SS. After getting input from dermatologists on the clinical requirements for diagnosis and monitoring, guidelines were developed to address flow cytometry instrument optimization, a recommended minimum antibody combination, assay design and optimization including how to assess for adequate staining intensity, and optimal strategies for analysis, interpretation, estimation of disease burden, and reporting. This presentation will discuss the guidelines developed, and illustrate some of the common pitfalls in the flow cytometric evaluation of peripheral blood for CTCL / SS.