ZNF217, a new member of the Krüppel-like family, is a transcription factor which interacts with co-repressors and histone-modifying proteins suggesting that ZNF217 may be part of a transcriptional repressor complex. ZNF217 may be an oncogene but little is known about the functions that ZNF217 could play. The aim of this work is to study the role of ZNF217 in tumor escape and its prognostic value in breast cancer. We showed that ZNF217 is associated with (i) increased proliferation in vitro and tumoral growth in vivo, (ii) stimulation of cell invasion and migration (iii) induction of EMT via the TGF-β pathway. Moreover, ZNF217-overexpressed cells are resistant to paclitaxel and ZNF217-induced resistance is associated with deregulated expression of the Bcl-2 family members and Aurora-A. Finally, we showed for the first time that high ZNF217 mRNA level is a novel marker of poor prognosis in breast cancer and is associated with the developpement of metastasis. Thus, ZNF217 seems to be important in mammary cancerogenesis. Clinical strategies targeting either ZNF217 directly or targeting ZNF217 mediators (eg Aurora-A or TGF-β) could be used for the treatment of breast cancer with ZNF217 overexpression