The expression of RANK and RANKL in HER2-positive breast cancer patients was analyzed by immunohistochemistry (IHC) in two independent sets of tissue microarrays (TMAs): a collection of HER2-positive tumor samples from treatment-naive patients (n = 197) and a cohort with tumors resistant to neoadjuvant trastuzumab-based chemotherapy (n = 43) from patients with residual invasive disease at surgery. This evidence concerns the gene TNFRSF11A and breast cancer.