Many treatments are used for epidermotropic cutaneous T cell lymphomas (CTCL) such as mycosis fungoides (MF) and Sézary syndrome (SS). All pretend to be effective, but none is really curative. As single drug therapy provides a response rate of about 55% with interferon alpha and about 45% with etretinate, we studied the effectiveness of combining these two drugs for immunomodulatory therapy in epidermotropic CTCL. A review of four reports, including a multicenter study performed in 45 patients, indicates a response rate of 56%, with better results for MF than SS. Side effects are generally moderate when low doses are used. The mechanism of action of this combined therapy on cutaneous lesions remains unclear. In vitro, a synergistic effect of retinoids on interferon alpha antiviral activity has been demonstrated, and in vivo an immunohistochemical study showed that the combined therapy modulates antigens expressed by keratinocytes and increases cytotoxic cells in dermis without modifying the number of Langerhans cells in epidermis.