We report a case of an invasive ductal breast carcinoma with significant heterogeneity: a HER-2+ tumor component was densely infiltrated by T-cells, whereas the HER2- tumor component, including two axillary lymph node metastases, showed much fewer tumor infiltrating lymphocytes. Array comparative genomic hybridization of dissected tumor cells from both components revealed many shared chromosomal aberrations but also unique alterations of the HER2+ tumor cell population besides HER2 amplification. We found a clonally dominated T-cell receptor rearrangement of the tumor infiltrating lymphocytes in the HER2+, but not in the HER2- tumor component. Thus, in this case HER2 overexpression is associated with a marked infiltration by T-cells suggesting a specific T-cell response against the HER2+ tumor cell population.