The commentary by Senitiroh Hakomori discusses the role of aberrant glycosylation in cancer malignancy. It highlights that glycosylation abnormalities are prevalent in various types of cancers and are often tumor-associated antigens. The debate on whether these abnormalities are a result or cause of cancer has been ongoing, with recent studies suggesting that they are both. Glycosylation plays a crucial role in promoting or inhibiting tumor cell invasion and metastasis, yet this area of research has received less attention compared to other topics like oncogenes and apoptosis. The article reviews several key glycosyl epitopes and their effects on tumor progression. For example, high expression of certain glycosyl epitopes like β6GlcNAc branching and sialyl-Tn promotes invasion and metastasis, leading to shorter survival rates. In contrast, other epitopes like β4GlcNAc and histo-blood group A suppress tumor progression, leading to higher survival rates. The mechanisms by which specific glycosyl epitopes induce invasive and metastatic phenotypes are not fully understood, but they are thought to affect processes such as apoptosis, motility, and angiogenesis. A notable study by Kakugawa et al. reports that enhanced expression of ganglioside-specific sialidase "Neu3" in colorectal cancer leads to the production of lactosylceramide (Lac-cer), which inhibits apoptosis. This finding opens new avenues for studying the function of gangliosides and glycosphingolipids (GSLs) in tumor progression. The commentary also discusses the complex interactions between glycosylation and various signaling pathways, such as those involving the EGF receptor tyrosine kinase and angiogenesis. Overall, the commentary emphasizes the importance of understanding the mechanisms by which glycosylation affects tumor cell phenotypes and suggests that targeting specific glycosyltransferases and glycosyl epitopes could be a promising approach for developing antitumor drugs.The commentary by Senitiroh Hakomori discusses the role of aberrant glycosylation in cancer malignancy. It highlights that glycosylation abnormalities are prevalent in various types of cancers and are often tumor-associated antigens. The debate on whether these abnormalities are a result or cause of cancer has been ongoing, with recent studies suggesting that they are both. Glycosylation plays a crucial role in promoting or inhibiting tumor cell invasion and metastasis, yet this area of research has received less attention compared to other topics like oncogenes and apoptosis. The article reviews several key glycosyl epitopes and their effects on tumor progression. For example, high expression of certain glycosyl epitopes like β6GlcNAc branching and sialyl-Tn promotes invasion and metastasis, leading to shorter survival rates. In contrast, other epitopes like β4GlcNAc and histo-blood group A suppress tumor progression, leading to higher survival rates. The mechanisms by which specific glycosyl epitopes induce invasive and metastatic phenotypes are not fully understood, but they are thought to affect processes such as apoptosis, motility, and angiogenesis. A notable study by Kakugawa et al. reports that enhanced expression of ganglioside-specific sialidase "Neu3" in colorectal cancer leads to the production of lactosylceramide (Lac-cer), which inhibits apoptosis. This finding opens new avenues for studying the function of gangliosides and glycosphingolipids (GSLs) in tumor progression. The commentary also discusses the complex interactions between glycosylation and various signaling pathways, such as those involving the EGF receptor tyrosine kinase and angiogenesis. Overall, the commentary emphasizes the importance of understanding the mechanisms by which glycosylation affects tumor cell phenotypes and suggests that targeting specific glycosyltransferases and glycosyl epitopes could be a promising approach for developing antitumor drugs.