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Critical appraisal of epigenetic regulation of galectins in cancer. Galectins are defined as the glycan-binding protein containing either one or two carbohydrate-binding domains and participate in various biological functions such as developmental processes, vascularisation programs, cell migration, and immune-regulation and apoptosis. Galectins are also linked to many diseases, including cancer. They are widely spread in extracellular and intracellular spaces, and their altered expression in cancer leads to tumor progression, metastasis, angiogenesis and stemness through different signalling pathways. Promoter methylation, microRNA, and histone modification constitute the epigenetic changes that regulate galectin activity in cancer. Our review discusses the concept of epigenetics in cancer and how the aforementioned factors i.e., promoter methylation, histone modification, change in miRNAs expression affect the glycomic changes in malignancies.