The efficiency of secondary tumor establishment is controlled by the ability of tumor cells to withstand a barrage of mechanical and immunological stresses during their passage through the circulatory system. Accumulating evidence suggests that the selectin-dependent interactions of circulating tumor cells with host cells promote their survival and extravasation from the vasculature, therefore representing a critical checkpoint for colonization of distant organs. These observations have motivated the identification and biochemical characterization of functional selectin ligands such as CD44 variant isoforms, carcinoembryonic antigen and podocalyxin-like protein, present on the surface of metastatic colon carcinoma cells. Understanding the molecular underpinnings of selectin-ligand interactions involved in heterotypic tumor cell-host cell adhesion events may provide guidelines for developing novel cancer diagnostics. Recent advancements in diagnostic device fabrication and design integrated with novel biomarkers exploiting the tissue specific biochemistry of malignant versus normal tissue-expressed selectin ligands may hold promise in providing effective alternatives to current cancer diagnostic technologies.