Syndecan-1 is a cell surface proteoglycan predominantly expressed on the surface of adult epithelial cells, and is normally present in all epidermal layers except for the most superficial terminally differentiated cells. Syndecan-1 mediates cell-cell and cell-extracellular matrix adhesion, thereby influencing cell morphology and growth characteristics. In addition, in vitro studies have shown that expression of syndecan-1 on tumor cells inhibits their invasion into the extracellular matrix. A total of 23 cutaneous biopsies of squamous cell carcinoma, including acantholytic squamous cell carcinoma, invasive squamous cell carcinoma which was not acantholytic, and squamous cell carcinoma in situ were examined for syndecan-1 immunoreactivity. The level of syndecan-1 expression was related to the degree of squamous cell dyshesion, with expression being greatest in the in situ lesions and least in the acantholytic lesions. The loss of syndecan-1 expression with increasing dyshesion of squamous cell carcinoma may he a mechanism for loosening of intercellular and cell-extracellular matrix attachments, thereby promoting the invasion of neoplastic cells into the dermis.