Tumor heterogeneity has been a stumbling block in the development of effective cancer treatments. Personalized medicine has evolved with the theory that matching therapies with the unique misregulated pathways often present in tumors will increase patient prognosis. Of particular interest is prediction or determination of the metastatic potential of a tumor. Thus, biomarkers that can predict metastases represent an enormous advance to our understanding over the clinical treatment of cancer. Considerable effort has been expended to characterize the cancer proteome for early detection, however, fewer efforts have been made to develop biomarkers to distinguish the potential for and the nature of metastasis. In this review, we discuss proteomic technologies as well as existing potential metastatic biomarkers for various cancers. In the conclusion, we discuss forward thinking as to what the field needs to enable translation to the clinic.