Histopathological and immunohistochemical studies were conducted to investigate the local existence and distribution of mast cells, fibroblasts or dendritic cells, and myofibroblasts in scleroderma, while paying particular attention to the interstices around the adnexa. The skin tissues in 15 cases of systemic scleroderma were classified histopathologically into three stages: early, fully developed, and late stage. Mesenchymal cells were distinguished immunohistochemically by 6 markers: tryptase, CD34, factor XIIIa, alpha smooth muscle actin (αSMA), vimentin, and desmin. In scleroderma, there was an increase in the number of tryptase-positive mast cells in the interstices around the adnexa. With no relation to the interstitial sites, there was a significant decrease in the number of CD34-positive cells in the late stage, and a significant increase in αSMA-positive cells in the fully developed stage, but a decrease in the late stage. Results of the present study brought about the following new findings: it was only in the mast cells that there was a significant difference in the cell distribution between the interstices around the adnexa and the interstices in non-adnexal sites. Secondly, it was suggested that mast cells, CD34-positive dendritic cells, and αSMA-positive myofibroblasts were involved in the fibrosis and shrinkage or disappearance of the adnexa when scleroderma developed.