Given that d16HER2 overexpression/activation drives a key oncogenic signal in HER2-positive BC and is considered a “flag” of HER2 addiction and trastuzumab susceptibility19,22,23, we hypothesized that such splice variant might play a crucial role also in other HER2-positive cancers, overall providing novel insights in the complex molecular landscape of HER2-driven tumors. This evidence concerns the gene ERBB2 and breast cancer.