Aberrant sialylation is closely associated with the malignant phenotype of cancer cells including metastatic potential and invasiveness. However, its biological significance and molecular mechanisms have yet to be fully elucidated. To determine causes and consequences, we have focused attention on mammalian sialidases, which cleave sialic acids from gangliosides and glycoproteins. The four types of human sialidases identified to date behave in different manners during carcinogenesis. One, found in the lysosomes, shows down-regulation in cancers, promoting anchorage-independent growth and contributing to metastatic ability, while another, found in the plasma membranes, exhibits marked up-regulation, resulting in suppression of apoptosis. The present review summarizes mostly our results on aberrant expression of sialidases and their possible roles in cancer progression.