This case series discusses 3 patients with long-standing eczematous or psoriasiform dermatitis, demonstrated by multiple biopsies. Following off-label treatment with dupilumab, all 3 patients had clinical expansion of disease, with histopathologic features consistent with cutaneous T-cell lymphoma (CTCL) on subsequent biopsy. We postulate that this expansion likely was secondary to an exacerbation of extant CTCL following exposure to dupilumab. A proposed mechanism of promotion of CTCL is based on the functional increase in IL-13 available for binding at the upregulated IL-13 receptor (IL-13R) α2 site on cells, following blockade of the α1 receptor with dupilumab. This progression merits further investigation.