All-trans retinoic acid (ATRA), an active metabolite of retinal, has been shown to exert anti-cancer activities in a number of cancer cells and tissues. Syndecan-1 is a proteoglycan, mediate cell-cell adhesion and prevent invasion in epithelial cells. The aim of the present study was to examine the level of syndecan-1 expression and the chemopreventive effect of ATRA during lung cancer development in BALB/c mice. Syndecan-1 expression was examined by immunohistochemistry using mouse monoclonal anti-human syndecan-1 antibody. In this study, benzo(α)pyrene [B(α)P] was used to induce lung cancer. The results indicated that ATRA has anti-cancer effect against B(α)P-induced lung tumor development as induced by number of tumor nodules and histopathologic report. The loss of syndecan-1 expression in the epithelial cell membrane is associated with tumor cell growth and invasiveness. Our study for syndecan-1 indicated a chemoprotective effect of ATRA against changes in lung epithelial cell membrane syndecan-1 expression in B(α)P-induced lung cancer model. Therefore ATRA could serve as effective chemotherapeutic agent against cancer invasion/metastasis, at least in the lungs.