The translationally controlled tumor protein (TCTP) plays a role in cell growth, cell cycle and cancer progression. TCTP controls negatively the stability of the p53 tumor suppressor protein and interacts with the cellular cytoskeleton. The deregulation of the actin and cytokeratin cytoskeleton is responsible for the increased migratory activity of tumor cells and is linked with poor patient outcome. Recent studies indicate that cyclin A,a key regulator of cell cycle, controls actin organization and negatively regulates cell motility via regulation of RhoA expression. We studied the organization of actin and cytokeratin cytoskeleton and the expression of TCTP, p53,cyclin A, RhoA and actin in HIO180 non-transformed ovarian epithelial cells, and OVCAR3 and SKOV3 (expressing low level of inducible p53) ovarian epithelial cancer cells with different metastatic potential. Immunostaining and ultrastructural analyses illustrated a dramatic difference in the organization of the cytokeratin and actin filaments in non-transformed versus cancer cell lines. We also determined that there is an inverse relationship between the level of TCTP/RhoA and actin/p53/cyclin A expression in ovarian cancer cell lines. This previously unidentified negative relationship between TCTP/RhoA and actin/p53/cyclin A may suggest that this interaction is linked with the high aggressiveness of ovarian cancers.