Various changes take place during the progression of cancer, some of which are favorable for tumor development and may help to escape the immunosurvillance. These include changes in the microenvironment around the developing tumor, which could be produced in response to phenotypic alterations or could modulate the expression of certain markers of tumor development. One such newly discovered molecule is HLA-G, which has been found to have immunosuppressive and immunomodulatory roles in the cancer development. The regulatory sequences, as seen, may be induced by various factors that may be present in tumor microenvironment. A recent study has investigated the antigen -G as a marker of susceptibility to chemotherapy. Further, its expression on tumors and how it can be exploited for diagnosis and therapy is discussed in this article.