Syndecans are a family of integral membrane proteoglycans that participate in cell-matrix interactions and growth factor binding. Syndecan-1 expression is induced during keratinocyte differentiation and reduced in squamous cell carcinomas. The purpose of this study was to examine the alteration in syndecan-1 expression in dysplastic oral epithelium. Sixty-six oral biopsy specimens (43 epithelial dysplasias, 3 carcinoma in situ and 20 squamous cell carcinomas) were studied using immunohistochemical methods. The normal epithelium specimens were highly positive for syndecan-1. Fifteen of 46 dysplasias or carcinoma in situ specimens showed negative or weak staining for syndecan-1, two of which were totally negative. intermediate and strong staining were observed in 17 and 14 dysplasias or carcinoma in situ specimens, respectively. Thirteen (65%) squamous cell carcinomas showed negative or weak staining for syndecan-1, seven of which were totally negative. Only three carcinomas had a strong syndecan-1 expression. Four of the 34 patients with dysplasia who were followed up developed squamous cell carcinoma. All these dysplasias had weak or totally negative syndecan-1 expression. The results suggest that the loss of syndecan-1 is associated with dysplastic changes in oral epithelium.