Endogenous lectins are cell receptors, expressed in normal and transformed cells both circulating as well as in organized tissues. Their biological significance was shown in developmentally regulated processes of cell migration, embryonic maturation, differentiation and during various other normal and pathological processes. This work will focus on the role of endogenous lectins and their glycoconjugate ligands in homing of circulating normal and cancer cells. During the normal immune process of lymphocyte recirculation and their journey among the whole body through the secondary lymphoid organs in the search for antigen, lectins are decisive molecules that allow the very first interaction of arrest onto the endothelial cell layer. It has been demonstrated that dual lectin-glycoconjugate interactions were taking part in the initiation of the whole adhesion cascade between adhering and endothelial cell. This indicates the role of the endothelium which will be described here. Indeed, using high endothelial cell lines immortalized by us, we could demonstrate that endothelium of microcapillaries is characterized by its tissue-specific properties although with a high microenvironment dependency. Both are decisive for selecting cells to stop and undergo further invasion. Such normal properties of endothelial cells and homing cells could be taken as example to understand pathologies like specific establishment of metastases in the case of cancer cells. Consequently, we shall take into account the potential offered by lectins and the knowledge of the structure of their ligand to design efficient adhesion blockers or enhancers as invasion inhibitors or immunomodulators.