Exome and targeted amplicon parallel sequencing in a patient with metastatic ER-positive and HER2-positive BC, receiving two lines of targeted therapy over three years, identified serial changes in circulating levels of sub-clonal private mutations, which correlated with different treatment responses between metastatic sites; this comparison of biopsy and plasma samples in a single patient showed that ctDNA allows real-time sampling of multifocal clonal evolution [13]. This evidence concerns the gene ERBB2 and breast cancer.