A 57-year-old woman was admitted to the UOC Lymphoproliferative Diseases in Rome on January 2018 with a 1-month history of itching, erythrodermia and lymphocytosis. A skin biopsy showed CD3 and CD4 positive cells and CD7 and CD26 negative cells. After the histological examination, an epidermotropic T-cell lymphoma was diagnosed. Laboratory test showed leukocytosis with Sezary cells, and flow cytometry of the peripheral blood a CD4/CD8 ratio >10 and 90% of CD4+ T-cells negative for CD7. CT scan showed supra- and sub-diaphragmatic lymph adenomegalies. These findings led to the diagnosis of SS, stage TNMB IV A1. From February 2018, the patient received a first-line treatment with interferon-alpha-2a 3 MUI twice a week, prednisone 10 mg/die and extracorporeal photopheresis. On September 2018, due to the worsening of the cutaneous disease, she underwent a second-line treatment with gemcitabine 1000 mg/m2 on days 1-8-15 every 28 days associated with extracorporeal photopheresis. In the meantime, we started the research for a matched unrelated donor, since she had not compatible related donor, considering the allogeneic transplantation: an HLA 10/10 possible MUD was found. On March 2020, the patient had a new cutaneous relapse and thus, a third line of treatment with mogamulizumab as bridge-to-transplant was administered. The dose schedule of mogamulizumab was 1 mg/kg once weekly for the first cycle, in a 28-day cycle, and then 1 mg/kg every two weeks, for a total of 11 cycles: at the end of the treatment, a complete response was obtained with a good tolerance. On February 2021, due to an aseptic necrosis of the head of the left femur that required arthroplasty, the patient discontinued the treatment. On September 2021, after 7 months from the discontinuation of mogamulizumab, blood tests, PET/CT and a new skin biopsy confirmed the persistence of the complete response. Therefore, on November 2021, the patient underwent allogeneic hematopoietic stem cells transplantation from matched unrelated donor HLA 10/10. She was admitted in our hospital and she started the conditioning therapy with TBF-RIC (thiotepa-fludarabine-busulfan) and a prophylaxis for GVHD with cyclosporine, methotrexate and thymoglobulin. The transplantation procedure had no complication and no sign of acute GVHD has been reported. The patient discontinued mogamulizumab one year ago, underwent stem cells transplantation and, after 3 months, a complete remission of SS still persists.