Several studies have investigated the possible involvement of viral agents, and among them herpes viruses, in the development of cutaneous T-cell lymphoma. The aim of our study was to determine whether T cells specific to Epstein-Barr virus (EBV) antigens were detectable among tumor-infiltrating lymphocytes infiltrating cutaneous lesions of a patient with Sézary syndrome. To analyze responses to EBV, we used a transient SV-40 origin-defective transformed simian cells transfection assay that permits an estimation of CD8 T-cell responses against a large number of HLA/viral protein combinations. This technique allowed the detection of EBV-specific T lymphocytes mainly directed against epitopes generated during the lytic cycle in the cutaneous lesions. This is, to our knowledge, the first description of the presence of EBV-specific T lymphocytes among tumor-infiltrating lymphocytes infiltrating the lesional skin of a patient with Sézary syndrome.