The aim of this study was to evaluate the influence of tamoxifen on the growth and aggregation behavior, focusing on the expression pattern of E-cadherin and beta-catenin, in oral squamous cell carcinoma (OSCC) in vitro. Oral squamous cancer cell lines (UM-SCC-14A, UM-SCC-14B and UM-SCC-14C) were treated with various concentrations of tamoxifen. Growth and aggregation behavior as well as the protein expression and its changes were analysed. All cell lines are estrogen receptor (ER) positive. Tamoxifen induced a significant growth inhibition and induced the ability to form cell aggregates. This phenomena was not accompanied by a change in E-cadherin or beta-catenin expression or due to transcriptional changes. beta-catenin showed isolated membrane staining and nuclear distribution in all cell lines. A defective Ecadherin/beta-catenin complex was seen in UM-SCC-14C with no restoration through tamoxifen treatment. The cell-cell formation is increased in all cell lines without any alterations in the functional and quantitative status of E-cadherin or beta-catenin, indicating that novel cell-cell adhesion complexes not involving the classical E-cadherin/beta-catenin influence cell growth and intercellular adhesion in OSCC.