The ZFX gene is an X-chromosome gene that contains 13 zinc fingers and is identical to the ZFY gene on the Y chromosome, save for 10 amino acids out of 393 total amino acids (3, 4). ZFX is required for embryonic stem cell (ESC) self-renewal (6). ZFX-deficient embryonic stem cells are incapable of self-renewal but retain their differentiation potential. ZFX is also required for the function and survival of hematopoietic stem cells (HSCs) (6). ZFX deficit in Tie2-Cre mice resulted in the loss of adult HSC, but residual knock-out HSC retained normal homing, egress, and erythromyeloid progenitor activity (6). However, complete knockouts were uncommon, indicating that there is significant selection against ZFX loss in the HSC (6). Primitive hematopoiesis was normal in the yolk sac of Tie2-Cre Zfx-decicient mice, demonstrating that ZFX is essential for adult hematopoiesis but not for primitive hematopoiesis (6). After injection with pIpC, mice reconstituted with Mx-Cre Zfx-deficient bone marrow lose their ability to produce B cells, T cells, granulocytes, dendritic cells, and the majority of NK cells, and there is a significant increase in Annexin-V positive apoptotic HSC, demonstrating that ZFX is required for self-renewal, maintenance, and survival of HSC in vivo (6). ZFX is a novel chemical that has the capacity to regulate both embryonic and hematopoietic stem cell features (6, 7). Throughout the hematological system, ZFX has been implicated in BCR-induced B-cell proliferation and survival (8). ZFX was also shown to be an inhibitor of acute T-lymphoblastic leukemia and myeloid leukemia differentiation (9), and was revealed to be required for imatinib resistance and proliferation of chronic myeloid leukemia cells (10). In non-hematopoietic malignancies, ZFX has been implicated in tumor development and cell proliferation in a number of solid tumors. Gastric cancer, gliomas and glioblastomas, squamous cell carcinomas of the tongue, pancreatic cancer, renal carcinoma, gallbladder cancer, and colorectal cancer are only a few examples (11-19). Three independent investigations concluded that elevated ZFX expression is pro-tumorigenic and/or promotes tumor development in breast cancer (20-22). According to one of these investigations, suppressing ZFX resulted in a reduction in breast cancer cell growth (20). Another investigation discovered a connection between increased ZFX expression and metastatic progression (21). A third research discovered that the long non-coding RNA was critical for triple negative breast cancer cells through ZFX suppression by microRNA 218. (22). On the other hand, our data demonstrate that increased ZFX expression is associated with improved survival outcomes, that ZFX is one of the most differentially expressed genes in those surviving stage IV metastatic cancer for more than 24 months, and that ZFX is expressed at higher levels in the primary and metastatic tumors of human breast cancer patients with a median survival of more than 24 months. According to one research, ZFX has a role in carcinogenesis via activating the Hedgehog pathway (23). ZFX has been shown to target histone genes (24) and the MHC-Class I HLA-11 promoter (25). ZFX expression differential expression in breast cancer should be verified at the protein level and in bigger and distinct cohorts of breast cancer patients. As we discovered that patients with better survival outcomes expressed greater levels of ZFX, the impact of imposed ZFX expression on tumor cell proliferation and viability in vitro and on tumor growth, metastasis, and survival in xenograft breast cancer models in vivo should be studied. In this investigation, we discovered that ZFX was one of the genes with the greatest quantitative difference in expression between tumors from patients with localized and metastatic breast cancer based on 24-month survival outcomes. ZFX expression was considerably increased in the main tumors of patients with breast cancer who had a disease-free survival of more than 24 months. ZFX expression was considerably increased in metastatic tumor tissues from stage IV metastatic breast cancer patients with an overall survival of more than 24 months. Our data together show that ZFX expression is related with improved survival outcomes in individuals with breast cancer, particularly those with metastatic breast cancer at stage IV. Modulating ZFX expression in breast cancer may be a logical treatment approach.