CTCL skin samples were collected with ethical approval and used for scRNA-seq, bulk sequencing, and IHC. Fresh skin biopsies underwent processing for single-cell suspensions, followed by FACS sorting and 10x Genomics Chromium loading. Library preparation and sequencing were conducted, and single-cell fixed RNA profiling was performed on FFPE samples. Whole-genome sequencing and Visium spatial transcriptomics were also detailed. Immunofluorescence staining, scRNA-seq data processing, and data clustering/integration were described. Differential abundance analysis, CNV inference, intratumor expression programs, subclustering, Visium processing, DEG analysis, bulk deconvolution, cell–cell interaction inference, and druggable target prediction were all part of the study. IHC for specific markers and statistical analysis were also included.