Dermatopontin is a tyrosine-rich acidic extracellular matrix protein of 22 kDa with possible functions in cell–matrix interactions and matrix assembly. We have previously isolated mRNAs expressed in hormone-refractory, but not in hormone-sensitive, mouse mammary cancer by comparing the mRNAs expressed in either tumor. A partial mRNA sequence isolated was later proven to be a part of mouse dermatopontin mRNA sequence. Transfectants of mouse dermatopontin cDNA into PC-3 human prostate cancer cells enhanced tumor growth when those were implanted subcutaneously in nude mice compared with the controls. Those transfectants showed a prominent stroma compared with the controls. Localization of the targets of a fusion protein of mouse dermatopontin and alkaline phosphatase was in the stroma of the PC-3 tumor tissues, but not in the tumor cells themselves. Additionally, we have established mouse dermatopontin transgenic mice under the control of the rat probasin promoter. The prostatic dorsal lobes of dermatopontin transgenic mouse showed prostate intra-epithelial neoplasia at the age of 11 months, but the control littermates did not. Epithelium of other prostatic lobes was not markedly different from that of the controls. In conclusion, dermatopontin may be involved in the pathogenesis and growth of the prostate cancer.