Although robust, these methods rely on highly standardized procedures that encompass all steps of FC, prior characterization of normal CD4+ T-cells from healthy donors and/or CTCL patients, and the use of multiparametric panels requirements typically only supported by reference centers. In this context, simplified FC strategy has been proposed, utilizing computationally enhanced data files (Seheult et al. 2024). However, the remarkable heterogeneity of SS, particularly the variability in the phenotype of SCs, which can evolve over time as the disease progresses, underscores the necessity of using more specific markers for their identification. This dynamic nature of SCs, characterized by shifts in immunophenotypic expression and clonal diversity, presents a challenge for accurate diagnosis and monitoring, making the application of advanced flow cytometry techniques and computational analysis crucial in clinical practice.