Cutaneous plasmacytosis is a rare disorder without systemic plasma cell proliferation in organs other than the skin, with a possible malignant transformation. However, there are few effective therapies available. It has been reported that interleukin-6 (IL-6), which is a cytokine inducing B-cell differentiation to immunoglobulin-producing cells, plays a part in systemic plasmacytosis. In this study, we performed intralesional steroid therapy in the lesions of cutaneous plasmacytosis in three patients, which resulted in sufficient clinical effects. We demonstrated that before treatment, plasma IL-6 levels were significantly elevated in all the patients, and that levels were reduced in parallel with the clinical improvement after therapy. Immunohistochemistry revealed IL-6 protein expression on tumour cells in the lesional skin. Reverse transcription—polymerase chain reaction (RT-PCR) detected IL-6 mRNA in the lesional skin in all cases, levels of which were decreased after the effective intralesional steroid therapy, but which were unchanged after ineffective topical photochemotherapy (PUVA). Peripheral blood mononuclear cells from the patients produced significantly large quantities of IL-6 which were reduced by addition of steroid in vitro. These results suggest that the generation of IL-6 plays the key role in cutaneous plasmacytosis and that intralesional steroid therapy is effective in reducing the production of IL-6 in this disorder.