p57 is a cyclin-dependent kinase (CDK) inhibitor, the first cell cycle regulator that is regulated by imprinting. p57 was initially considered to be a tumor suppressor based on its ability to regulate cell cycle progression through its N-terminal domain. Now, it has been found that p57 is also involved in the regulation of other cellular processes including transcription, apoptosis, differentiation, development, and migration via its PAPA repeat and carboxyl-terminal domain. The multifunction of p57 participate in many processes in tumorigenesis involving in different mechanisms including loss of imprinting, loss of heterozygosity, promoter methylation, histone deacetylation and regulation of microRNAs. Moreover, upstream signaling pathways, protein-protein interactions and altered subcellular localization have also been reported to participate in abnormal expression of p57 resulting in the occurrence and progression of cancer. However, it is unclear whether p57 may play a dual role during tumorigenesis under different cellular processes similarly to its siblings. The presence of a nuclear localization signal in p57 is intriguing because it may affect the subcellular localization of p57, which can result in abnormal proliferation and motility of cells, and may be oncogenic under certain circumstances, as observed for p21 and p27.