Polymorphic human major histocompatibility complex (MHC) genes are pivotal to the functioning immune system, and strong autoimmune disease associations with human leukocyte antigens (HLAs) have been established, although the precise mechanisms of these associations are not fully defined. There is now clear evidence of immunosurveillance in cancer, thus it seems reasonable to hypothesize that HLA types might predispose some individuals to particular malignancies. In addition, HLAs could influence the susceptibility or progression of a malignancy, and this might be most apparent in virally associated cancers. This article discusses the results and problems of searching for such HLAs and cancer associations. To date, it appears that no strong associations between HLAs and cancer risk exist.