Abstract: The human epidermal growth factor receptor 2 (HER2) oncoprotein is overexpressed in about 18% to 20% of breast cancers, and HER2 gene amplification is responsible for protein overexpression in most cases. A small subset of cases show an increase in centromere 17 copy numbers without HER2 amplification, commonly referred to as polysomy. Although HER2 overexpression is an established adverse prognostic factor in breast cancer, there are conflicting results about adverse prognostic factors in cases with increased numbers of centromere 17 copies without HER2 amplification. Whereas most patients with increased centromere 17 copy numbers are HER2 2+ by immunohistochemistry, a minority are 3+. Currently, patients with increase in centromere 17 copy numbers without HER2 amplification are treated similar to patients who show neither amplification nor polysomy. Recent studies have demonstrated that what is commonly referred to as chromosome 17 polysomy is not true polysomy of chromosome 17, but often due to CEP17 duplication or amplification, or due to gains or amplification in the pericentromeric region of chromosome 17. Therefore, it is believed that use of CEP17 to correct HER2 copy numbers might not be ideal and may give misleading results. The case presented highlights a conundrum where, by absolute HER2 copy numbers, the case would be HER2 amplified, and by HER2/CEP17 ratio it is not amplified. In this context, we discuss HER2 amplification and centromere 17 copy number alterations in invasive breast cancer.