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Increased T-cell cytoplasmic IL-4 is more frequent in late CTCL stages, correlates with T-cell immunophenotype changes found in advanced disease and is associated with clonality. Increased cytoplasmic IL-4 is frequent both in erythrodermic MF and SS patients, in contrast to other variables found increased only in SS, suggesting that IL-4 may be an early indicator of disease progression. Moreover, our results show that increased cytoplasmic IL-4 is the sole predictor of advanced CTCL disease and confirm the relevance of FC determination of IL-4 in the routine evaluation of CTCL cases.