The human epidermal growth factor receptor 2 (HER2) oncoprotein is overexpressed in about 20% of breast cancers, with HER2 gene amplification responsible for protein overexpression in the vast majority of patients. A subset of breast cancers have chromosome 17 aneusomy, due to either 17 monosomy (a single copy of chromosome 17) or polysomy (increased copy numbers of chromosome 17). Although HER2 overexpression is an established adverse prognostic factor in breast cancer, the role of unamplified chromosome 17 polysomy is uncertain and there is a paucity of literature on the correlation of chromosome 17 aneusomy with important prognostic and predictive pathologic factors in invasive breast carcinoma. Furthermore, while patients showing HER2 amplification with or without polysomy 17 are treated with trastuzumab with or without other chemotherapy, treatment of patients with unamplified chromosome 17 polysomy is not well defined. Currently most of these patients are treated similar to patients with neither amplification nor 17 polysomy. The aim of this study was to compare some prognostic and predictive factors in invasive breast carcinoma in patients with unamplified chromosome 17 polysomy with that seen in cases with HER2 gene amplification and those with neither amplification or polysomy. We found that invasive breast carcinomas with unamplified chromosome 17 polysomy are associated with several adverse prognostic indicators such as a higher nuclear grade, mitotic activity, Nottingham score, histologic grade, tumor stage, and greater estrogen receptor negativity with a trend towards the amplified group, in contrast to patients with neither amplification or polysomy. Although most patients with unamplified 17 polysomy have a 2+ equivocal score on immunohistochemistry, a minority has a 3+ positive score. An increased adverse role for unamplified polysomy along with 3+ protein expression in some patients supports the idea that these patients should be considered for therapy with trastuzumab and/or anthracyclines.