Background: Idiopathic cutaneous calcification and ossification occur in the absence of an abnormal serum calcium level or pre-existing tissue abnormality. The pathogenesis has not been fully elucidated. The aim of this study was to investigate the expression of several molecular mediators in the idiopathic cutaneous calcification and ossification. Methods: Immunohistochemical study was used to evaluate the expression of molecular mediators, bone morphogenetic protein 4 (BMP-4), β-catenin, osteopontin, osteonectin and osteocalcin, and cell markers, smooth muscle actin, CD29 and CD44. And confocal laser scanning microscopy was used to evaluate the colocalization of BMP-4 and BMP receptor type IA. Results: BMP-4, β-catenin, osteopontin, osteonectin and osteocalcin were expressed on the calcified and ossified tissue. Especially, BMP-4 was expressed on the surrounding mesenchymal cells. Smooth muscle actin positive mesenchymal cells were on around the immature ossified tissue. Mesenchymal stem cell markers, CD29 and CD44 were not expressed. Conclusion: Our data suggest that BMP-4, β-catenin, osteopontin, osteonectin and osteocalcin may be involved in the idiopathic cutaneous calcification and ossification. And smooth muscle actin positive mesenchymal cells may be involved in the cutaneous ossification. This study suggests that the idiopathic cutaneous calcification and ossification is highly complicated and regulated active process like ectopic calcification of other tissues.