Objective To investigate the clinicopathologic features and immunophenotype of primary squamous cell carcinoma of the breast (PSCCB) with HER2 overexpression. Methods Two cases of PSCCB with HER2 overexpression were retrospectively reviewed, and the pathological features, immunophenotype and prognosis were discussed. Results The tumor showed malignant squamous cells arranged in sheets, groups and nests, forming keratin-pearl and intercellular bridges. Immunohistochemical (IHC) analysis showed that the tumor cells were positive for 34 beta E12, p63, CK5/6, E-cadherin and P120, while negative for ER and PR. Furthermore, HER2 overexpression showed strong continuous expression in cell membrane with a score of 3+ by IHC, or amplification by FISH. Conclusions PSCCB is a rare tumor in breast cancer and HER2 overexpression is rather unusual in PSCCB. The diagnosis mainly depends on the clinicopathologic features together with the immunophenotype. HER2 positive indicates poor prognosis. However, targeted therapy for HER2 may be a new hope for patients.