A retrospective analysis of primary breast tumors revealed that patients with high <i>ZNF217-ΔE4</i> mRNA levels had a higher risk of developing bone metastases.<h4>Conclusions</h4>Overall, this study identifies ZNF217-ΔE4 as a novel functional isoform that mediates breast cancer cell aggressiveness and bone marrow homing. This evidence concerns the gene ZNF217 and breast cancer.