Approximately 88% of cutaneous T-cell lymphoma (CTCL) patients are affected by pruritus that responds poorly to current antipruritic therapies. Interleukin (IL)-31, a Th2 cytokine, has been found to be increased in the serum of CTCL patients and to correlate with itch severity. This study investigated the role of IL-31 and its receptors (IL-31 receptor-alpha [IL-31RA] and OSMRβ) in the skin of CTCL patients with mild versus moderate/severe pruritus. Expression levels of IL-31, IL-31RA, and OSMRβ in the skin were measured using immunohistochemistry and correlated to pruritus severity and disease stage. In CTCL patients with moderate/severe pruritus, IL-31 was significantly elevated in the epidermis and dermal infiltrate, while IL-31RA and OSMRβ were significantly elevated only in the epidermis. Furthermore, epidermal IL-31 levels correlated to itch severity. These results show that IL-31 may play a role in CTCL pruritus by exerting indirect effects on sensory nerves through epidermal neoplastic T cells and keratinocytes to transmit itch.