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Siglecs are widely expressed on leucocytes and bind to ubiquitously presented glycans containing sialic acids (sialoglycans). Most Siglecs carry an immunoreceptor tyrosine‐based inhibition motif (ITIM) and elicit an inhibitory intracellular signal upon ligand binding. A few Siglec receptors can, however, recruit immunoreceptor tyrosine‐based activation motif (ITAM)‐containing factors, which activate cells. The role of hypersialylation (the enhanced expression of sialoglycans) has recently been explored in cancer progression. Mechanistic studies have shown that hypersialylation on cancer cells can engage inhibitory Siglecs on the surface of immune cells and induce immunosuppression. These recent studies strongly suggest that the Siglec–sialic acid axis can act as a potential target for cancer immunotherapy. Moreover, the use of new tools and techniques is facilitating these studies. In this review, we …