Skin hyperpigmentation and itching are characteristic findings in systemic sclerosis (SSC) patients. Stem cell factor (SCF, c-kit ligand) is a multifunctional cytokine which can promote melanocyte and mast cell development. We investigated the SCF expression histopathologically in normal and SSC skin, and compared the expression with the serum SCF levels measured with a specific enzyme-linked immunosorbent assay. The epidermal and dermal immunoreactive SCF expression was markedly higher in the forearm skin of edematous phase SSC patients than in that of normal subjects. Tissue SCF expression declined from the sclerotic phase to the atrophic phase, where it was close to the normal level. In contrast, the elevated serum SCF level seen in the edematous phase samples was further increased in the sclerotic phase samples. The serum SCF level decreased in the atrophic phase, but it still remained at a level higher than that of the normal controls. Itching and increase of dermal mast cell number are characteristic of edematous phase SSC, and are in bears a parallel to the presently observed dermal SCF expression profile. Pigmentation is significant in sclerotic phase SSC and lasts to the atrophic phase, which may correspond to the serum SCF level observed here. These results indicate a contribution of the fibroblast membrane integral SCF in dermal mast cell development, and of the soluble serum SCF to melanocyte activation in SSC.