The siRNA/shRNA-mediated knockdown of the NSDHL gene inhibited spheroid formation of ER + breast cancer cells grown on ultra-low attachment plates and tumorigenesis in an orthotopic breast cancer mouse model, leading to a reduction in BCSCs/progenitors with CD44+/ CD24- and EpCAM+/CD49f + phenotypes, and high ALDH activity in MCF-7 spheroids and xenograft tumors. Here, NSDHL is linked to breast carcinoma.