Invasion and metastatic spread of malignant neoplasms are associated with active locomotion of tumor cells. This locomotion occurs at the site of the primary growth, as well as at both the entrance to and the egress from blood vessels. Some factors derived from host tissues have been shown to stimulate the intrinsic motility of tumor cells in in vitro studies. These factors are believed to influence both the extent and the direction of tumor cell movement in vivo to specific target organs. Although much experimental research has been done to observe this phenomenon, the detailed molecular kinetics and biomechanical functions of the generation of cell locomotion have not been well understood, such as initiation and regulation of pseudopod formation under certain chemoattractants. We are developing mathematical models through a biophysical approach, based on both molecular and continuum mechanics theories, to understand the mechanism of this metastatic spread.