The cellular prion protein (PrP (c)) is a glycoprotein anchored to the cell surface by glycosylphosphatidylinositol (GPI). PrP (c) is expressed both in the brain and in peripheral tissues. Investigations on PrP (c)'s functions revealed its direct involvement in neurodegenerative and prion diseases, as well as in various physiological processes such as anti-oxidative functions, copper homeostasis, trans-membrane signaling, and cell adhesion. Recent findings have revealed the ectopic expression of PrP (c) in various cancers including gastric, melanoma, breast, colorectal, pancreatic, as well as rare cancers, where PrP (c) promotes cellular migration and invasion, tumor growth, and metastasis. Through its downstream signaling, PrP (c) has also been reported to be involved in resistance to chemotherapy and tumor cell apoptosis. This review summarizes the variance of expression of PrP (c) in different types of cancers and discusses its roles in their development and progression, as well as its use as a potential target to treat such cancers.