Cases of breast cancer showing human epidermal growth factor receptor-2 (HER-2) protein overexpression without corresponding gene amplification have been found in immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) results. We investigated the clinicopathological characteristics of cases showing HER-2 protein overexpression breast cancer without gene amplification (IHC3+/FISH-) and compared them to cases showing HER-2 protein overexpression breast cancer with gene amplification (IHC3+/FISH+). This study was conducted on 90 patients with HER-2 IHC3+ breast cancer. The clinicopathological factors analyzed included tumor size, histological grade, nuclear grade, nodal involvement, and hormone receptor status. HER-2 IHC3+/FISH- breast cancer was found in 14 of 84 tumors (16.7%) and showed a statistically significant lower histological and nuclear grade (P = .000) and higher expression of estrogen receptors (ERs) and progesterone receptors (PRs) (P = .006) than IHC3+/FISH+ breast cancer. In conclusion, HER-2 IHC3+/FISH- breast cancer could be a subgroup showing lower histological/nuclear grade and higher expression of ERs/PRs.