BORIS (CTCFL) is a DNA binding protein which is involved in tumorigenesis. Although, there are diferent opinions on the level of gene expression and function of BORIS in normal and cancer tissues, the results of many studies have classifed BORIS as a protein belonging to cancer/testis (CT) genes, which are identifed as a group of genes that are expressed normally in testis, and abnormally in various types of cancers. In testis, BORIS induces the expression of some male germ cell/testis specifc genes, and plays crucial roles during spermatogenesis and production of sperm. In tumorigenesis, the role of BORIS in the expression induction of some CT genes and oncogenes, as well as increasing proliferation/viability of cancer cells has been demonstrated in many researches. In addition to cancer cells, some believe that BORIS is also expressed in normal conditions and plays a universal function in cell division and regulation of genes. The following is a comprehensive review on contradictory views on the expression pattern and biological function of BORIS in normal, as well as cancer cells/tissues, and presents some evidence that support the expression of BORIS in cancer stem cells (CSCs) and advanced stage/poorer diferentiation grade of cancers. Boris is involved in the regulation of CSC cellular and molecular features such as self-renewal, chemo-resistance, tumorigenicity, sphereforming ability, and migration capacity. Finally, the role of BORIS in regulating two important signaling pathways including Wnt/β-catenin and Notch in CSCs, and its ability in recruiting transcription factors or chromatin-remodeling proteins to induce tumorigenesis is discussed.

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