As a result of extensive studies over the past three decades, it is now evident that first, IFN-γ can facilitate tumor initiation and, subsequently, promote changes in tumor cell phenotype towards increased fitness for growth in immunocompetent host; and second, that it is intimately involved in several homeostatic or cancer-triggered mechanisms that promote establishment of immunosuppressive tumor microenvironment (Figure 1). This evidence concerns the gene IFNG and cancer.