Homeobox genes are critical in tumor development. An isoform protein of DLX4 called BP1 is expressed in 80% of invasive ductal breast carcinomas. BP1 overexpression is implicated in an aggressive phenotype and poor prognosis. BP1 upregulation is associated with estrogen receptor negativity so those tumors do not respond to antiestrogens. Breast cancer is the second leading cause of death in women. BP1 could serve as both a novel prognostic biomarker for breast cancer and a therapeutic target. In this review, we address the role of BP1 protein in tumorigenesis of breast cancer and four other malignancies. A number of functions of BP1 in cancer are also discussed. Female breast cancer represents 14.6% of all new cancer cases in the USA according to the National Cancer Institute [1]. An estimated 252,710 new cases of invasive breast cancer are expected to be diagnosed in women in the USA in 2017. It is also estimated that 30% of newly diagnosed cancers in women will be breast cancers [2].Breast cancer is a hormone-dependent cancer, and estrogen (17β-estradiol) plays a critical role in the initiation and the progression of this disease [3]. Estrogen, produced by the ovaries, affects the growth and function of mammary glands by binding to the estrogen receptors (ERs) α and β. Through dimerization of the receptor, translocation to the nucleus and interaction with estrogen response elements in the promoter region of targeted genes, gene expression leads to multiple biological outcomes [4]. 70% of invasive breast cancers are ER positive (ER + ), making antiestrogens essential in treating these patients [5]. Targeting the ER or its pathway using tamoxifen (a selective ER modulator) or fulvestrant (an ER downregulator) have been successful therapeutic strategies [6]. However, drug resistance remains a major challenge in treating breast cancer. The main pathway leading to resistance involves loss of ER expression or selection of an ER-negative population of cells. Moreover, these ER-negative breast cancers have a higher histologic grade and a higher proliferative rate and are associated with poorer prognosis. This highlights the key importance of finding alternative targets to treat these patients and identifying a new biomarker for breast cancer prognosis.BP1 protein, an isoform of DLX4, belongs to the homeobox gene family which includes regulatory genes implicated in early development and cell differentiation that are frequently dysregulated in cancer [7]. Therefore, targeting BP1 may provide a new avenue for breast cancer management. The first related paper was published in 1998, when the authors mapped this new homeobox gene to chromosome 17q21 and characterized its role in repression of the β-globin gene [8]. During the last 20 years, several studies have been carried out to measure BP1 levels in breast cancer and other carcinomas, with the primary aim of confirming its diagnostic and prognostic value as a biomarker. We are writing this review to consolidate and update all of the available information on BP1. Homeobox...