Under normal conditions, Stat proteins are only transiently activated but genetic alterations, epigenetic changes, persistent cytokine signaling, and infections appear to drive constitutive activation of Stat3, Stat5, and Stat6 signaling in the malignant T cells during the clinical course of CTCL [19, 21, 24, 41, 43, 77–83]. The gene discussed is STAT3; the disease is primary cutaneous T-cell non-Hodgkin lymphoma.