Stathmin is a microtubule-destabilizing phosphoprotein, firstly identified as the downstream target of many signal transduction pathways. Several studies then indicated that stathmin is overexpressed in many types of human malignancies, thus deserving the name of Oncoprotein 18 (Op18). At molecular level, stathmin depolymerizes microtubules by either sequestering free tubulin dimers or directly inducing microtubule-catastrophe. A crucial role for stathmin in the control of mitosis has been proposed, since both its overexpression and its downregulation induce failure in the correct completion of cell division. Accordingly, stathmin is an important target of the main regulator of M phase, cyclin-dependent kinase 1. Recent evidences support a role for stathmin in the regulation of cell growth and motility, both in vitro and in vivo, and indicate its involvement in advanced, invasive and metastatic cancer more than in primary tumors. Many studies suggest that high stathmin expression levels in cancer negatively influence the response to microtubule-targeting drugs. These notions together with the fact that stathmin is expressed at very low levels in most adult tissues strongly support the use of stathmin as marker of prognosis and as target for novel anti-tumoral and anti-metastatic therapies.