Leukemia inhibitory factor (LIF) is a polyfunctional cytokine with a variety and a diverse range of biological activities. However, this is a reflection of the fact that the cytokine is expressed in many different tissues, has a wide target cell range, and fulfills different functions in different tissues. The purpose of this article is to examine what is known about LIF expression in the skin and to consider whether LIF plays a role in inflammatory and hyperplastic events in the skin. LIF is strongly expressed in skin tumors, and recent studies indicate that it may affect tumor growth by several different mechanisms. The biological activities of LIF relevant to carcinogenesis, its expression, and signal transduction by the LIF receptor are described. Expression of LIF in normal skin by skin tumors and its induction by ultraviolet radiation and proinflammatory stimuli are discussed, as are possible interactions between LIF, mast cells, and tumor growth. We consider what role LIF and other members of the hemopoietin family of cytokines play in healthy and diseased skin and whether LIF could play a role in hyperplastic skin disorders. LIF appears to be an important cytokine for normal keratinocyte growth and wound healing and may be involved in regulating the proliferation of skin tumors. Accordingly, LIF may be a useful target for anticancer therapy and as a growth factor for normal skin during reconstructive surgery.