We report a case of a patient who developed a central nervous system (CNS) metastasis 17 months after surgery and adjuvant therapy for stage II breast cancer. The HER2 status of the primary tumor as determined by immunohistochemistry (IHC) was 1+, and fluorescence in situ hybridization (FISH) performed retrospectively showed a borderline-negative result (ratio, 1:9), although HER2 amplification was present in a minority of breast cancer cells. By contrast, the HER2 status of the CNS metastasis was positive by IHC (3+) and FISH (ratio, 3:7). This report discusses the possibility that, for metastatic invasion into the CNS, clonal selection may occur, favoring HER2-positive cell clones.