HLA-G is a nonclassic MHC class I molecule that functions as an immunomodulatory molecule;which has a direct inhibitory effect on immune responses and induces the generation of suppressor or regulatory cells. The relevance of HLA-G in various pathologic conditions, such as transplantation, autoimmunity and infectious and malignant diseases, has been extensively investigated. In the context of hematologic malignancies, such as acute myeloid leukemia, chronic lymphocytic leukemia and lymphoma, the expression and clinical significance of HLA-G was discussed; however, interpretation remains controversial. In this review, we summarize HLA-G expression in hematologic malignancies and emphasize the clinical relevance of this expression to disease progression. The possible mechanism involved in HLA-G expression regulation is also highlighted.