Sialic acid is a code for “recognize-me-as-self” (a “see-me-as-self” signal) on cells or molecules for immune cells that survey non-self-items. One of the mechanisms in discrimination of self- and non-self-items is the presence of sialic acid-binding immunoglobulin-like lectins (SIGLECs) on the immune cell surface. SIGLECs have a dual role with respect to host cells in the innate immune system. Under normal conditions, the ability of SIGLECs to discriminate non-self from self is important in inhibiting attacks on the self-cells. However, cancer cells and sometimes bacterial cells can misuse this system, using more sialic acid to cheat immune cells, as if they are self-cells, resulting in escape from the host immune system. SIGLEC-7 is an important inhibitory receptor predominantly expressed in natural killer cells. The ligand specificity of SIGLEC-7 is diverse and complex, and its surveillance mechanisms are unclear. In this chapter, we focus on ligand specificity from two perspectives. One is the clustering effect of the ligand on SIGLEC-7, and the other is a new sialic acid-binding site in addition to that previously discovered in SIGLEC-7. These perspectives inform the decoding of true biological contexts within the SIGLEC-sialic acid axis.