Epithelial protein lost in neoplasm-alpha (EPLIN-alpha) is a cytoskeletal protein whose expression is often lost or is aberrant in cancerous cells and tissues and whose loss is believed to be involved in aggressive phenotypes. This study examined this molecule in human epithelial ovarian tissues and investigated the cellular impact of EPLIN-alpha on ovarian cancer cells (EOC), SKOV3 and COV504. The expression of EPLIN-alpha in human ovarian tissues and EOC was assessed at both the mRNA and protein levels using reverse transcription-PCR (RT-PCR) and immunohistochemistry, respectively. In vitro assays for cellular matrix adhesion and migration (confirmed by an electrical cell substrate impedance sensing (ECIS) based method), invasion and cell growth were employed in order to assess the biological influence of EPLIN-alpha expression on EOC cells. Immunohistochemical analysis of ovarian cancer samples demonstrated that only a small number expressed EPLIN-alpha protein. Downregulation of EPLIN-alpha protein in EOC cell lines increased the growth, invasion, adhesion and migration in vitro. This EPLIN-alpha downregulation may have a prognostic value. From these data, we conclude that down regulation of EPLIN-alpha may be associated with poorer patient prognosis, and that this molecule appears to play a tumour suppressor role by inhibition of EOC growth and migration.