JC virus (JCV) is a human polyomavirus of the Polyomaviridae family, which also includes BK virus and simian vacuolating virus 40 (SV40). JC virus was first isolated in 1971 from the brain of a patient with Progressive Multifocal Leukoencephalopathy (PML). Like other polyomaviruses, JCV has a restricted host range. The virus infects the majority of the human population with seroconversion occurring during adolescence. JCV has a limited and specific tissue tropism infecting the kidney and oligodendrocytes and astrocytes in the central nervous system (CNS). Initial JCV infection is generally asymptomatic in immunocompetent hosts, and it establishes a persistent infection in the kidney and possibly bone marrow. In immunocompromised individuals JCV can cause a lytic infection in the CNS and lead to development of the fatal, demyelinating disease PML. The name polyoma is derived from the Greek terms: poly, meaning many, and oma, meaning tumors, owing to the capacity of this group of viruses to cause tumors. JCV inoculation of small animal models and non-human primates, which are not permissive to a productive JCV infection, leads to tumor formation. Given the ubiquitous nature of the virus and its strong association with cancer in animal models, it is hypothesized that JCV plays a role in human cancers. However, the role for JCV in human cancers and tumor formation is not clear. Some researchers have reported an association of JCV with human cancers including brain tumors, colorectal cancers, and cancers of the gastrointestinal tract, while other groups report no correlation. Here, we review the role of JCV in cancers in animal models and present the findings on JCV in human cancers.