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The persistence of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients is associated with poor prognosis. Preliminary studies indicated that these patients might benefit from secondary adjuvant targeted therapy. HER2 protein is suggested as one of the most promising targets. The aims of this study were (1) to determine the HER2 status of DTC in BM of breast cancer patients and (2) to compare the HER2 status of DTC and corresponding primary tumors.BM aspirates from 137 primary breast cancer patients were included into the study. A double staining procedure was used for the identification of cytokeratin-positive (CK)/HER2 positive cells. HER2 status of the primary tumor was immunohistochemically assessed by the HERCEP-test™.In 46 of 137 (34%) breast cancer patients CK-positive cells were detectable in BM. DTC with HER2 positivity were found in 20 (43%) of these patients. The HER2 expression on DTC was heterogeneous in 7 of 17 (41%) patients. Concordance rate of HER2 status between primary tumor and DTC was 62%. In 12 of 20 patients with HER2 negative tumors HER2 positive DTC were detected.HER2 positive DTC can be detected in patients with HER2 negative primary tumors. Therefore, the antigenic profile of DTC may be considered for treatment decision since these patients might actually benefit from trastuzumab. However, the HER2 overexpression on DTC is heterogeneous in individual patients which may reduce the efficacy of an immunotherapy based strategy directed against HER2-antigen only.