The aims of this study were i) to define the repertoire of somatic genetic alterations in primary HER2-positive breast cancers and their corresponding brain metastases in patients whose lesions metastatic to the brain were collected at rapid post-mortem examination or surgical excision of the brain metastases, ii) to analyze the temporal heterogeneity involved in the progression of HER2-positive breast cancers to brain metastasis, and iii) to identify potential clinically actionable alterations that may allow targeting brain metastasis in HER2-positive breast cancer patients. This evidence concerns the gene ERBB2 and breast cancer.