Background: Since soluble intercellular adhesion molecules 1 (sICAM-1) retain their ability to bind to their ligand, they can interfere in cell-mediated immunosurveillance. Objective: We studied the impact of various cytokines on ICAM-1 release of several tumor cell lines. Methods: Two melanoma cell lines (M19, M26), 1 B lymphoblastoid cell line (Daudi), 1 erythroleukemia cell line (K562), 1 Sézary-cell-derived cell line (SeAx), 1 cell line derived from a mycosis fungoides lesion (MyLa) and normal peripheral blood mononuclear cells (PBMC) were grown in the presence of interferon γ (IFN-γ), IFN-α, interleukin-2 (IL-2), IL-6 and tumor necrosis factor α (TNF-α) in various concentrations. ICAM-1 release into the supernatant was measured after 24 and 48 h using an enzyme-linked immunosorbent assay (ELISA). Results: PBMC and the B lymphoblastoid cell line did not shed detectable amounts of sICAM-1. In all other cell lines, ICAM-1 shedding was found with and without cytokine stimulation. In all cell cell lines except the CTCL-derived one, ICAM-1 shedding was marginally affected by IFN-α, IL-2 and IL-6. TNF-α and IFN-γ enhanced the shedding in a time- and dose-dependent manner. In the SeAx line, IL-2 and IFN-γ inhibited ICAM-1 release. By contrast, TNF-α and IL-6 enhanced it. The CTCL-derived MyLa responded to IFN-α with a dose-dependent increase in ICAM-1 shedding. All other cytokines had marginal influence. Conclusion: Cytokine-modulated ICAM-1 shedding shows quantitative and qualitative differences in the investigated cell lines. This might have implications for the pathophysiology of cutaneous malignancies and their susceptibility to immunotherapies.