We performed largescale gene-expression profiling in patients with mycosis fungoides (MF), and to our surprise we found that B-cells were significantly upregulated in the microenvironment in MF compared to controls. We could confirm the presence of B-cells in situ and this raised a number of important questions. How does the infiltrating B-cells impact MF biology, and do they have a role in disease progression? Can we re-establish immunological tumor control by targeting B-cells therapeutically? Further studies are required to elucidate the role of B-cells in MF and our group have initiated several investigations exploring the nature of B-cell infiltration in MF.