Mesenchymal support plays crucial roles in both normal and cancer tissue development. In the skin, dermal mesenchymal fibroblasts provide keratinocytes with many cytokines as critical crosstalk molecules through epithelial-mesenchymal interactions. A number of reports have demonstrated that mesenchymal stem cells and myofibroblasts participate in skin repair. Although the importance of both mesenchymal support and the mesenchymal cell phenotype has been recognized, the relationship between the mesenchymal cell phenotype and the paracrine/autocrine action remains unclear. Moreover, the organ that supplies these supportive mesenchymal cell types within the injured tissue is still unclear. In the skin, it is also unknown whether non-skin organ-derived mesenchymal cells, other than the bone marrow and adipose tissue, affect epidermal regeneration through mesenchymal-epithelial interactions. Here, we highlight recent findings regarding the paracrine/autocrine action and phenotypic characters of non-skin-derived mesenchymal cells. We also briefly present our preliminary data regarding the supporting effect of cancer-associated fibroblasts on normal tissue repair.