Mycosis fungoides (MF) is the most common variant of cutaneous T-cell lymphoma (CTCL). MF is characterized by chronic inflammation dominated by cluster of differentiation 4-positive (CD4(+)) T-cells and T helper 2 cytokines, and as the malignant T-cell clone is initially elusive, early diagnosis is often impossible. MF usually takes an indolent course, but for unknown reasons may turn into an aggressive disease with a poor prognosis. Herein, we used a global quantitative real-time polymerase chain reaction platform to study microRNA (miR) expression in patients with early MF (n=13), more advanced CTCL (n=42), and atopic dermatitis (AD, n=20). Thirty-eight miRs were differentially expressed (≥2-fold) in early MF vs. AD and 36 in early MF vs. more advanced disease. miRs that distinguish early MF from AD included both up-regulated (miR-155, miR-146a, 146b-5p, miR-342-3p, let-7i*) and down-regulated (miR-203, miR-205) miRs previously implicated in advanced CTCL. When comparing early MF to more advanced CTCL, additional miRs were significantly up-regulated including miRs which are part of the oncogenic miR-17/92, 106b/25 and 106a/363 clusters. In 16 patients for whom detailed follow-up data were available, 72 miRs were found differentially expressed between patients with progressive vs. those with non-progressive disease, again including miRs with a known relevance for lymphomagenesis, e.g. miR-155, miR-21, let-7i, miR-16, miR-142-3p, miR-146b-5p, miR-92a, miR-93 and miR-106a. In conclusion, we showed that early MF and AD display very different miR profiles despite their clinical, histological, and immunological similarities. During progression, an additional set of miRs becomes deregulated, suggesting their role in disease progression. These data suggest that miR profiling in CTCL may be a key to improving both diagnosis and risk prediction.