Rationale: Primary squamous cell carcinoma (PSCC) of the breast is one of the least common types of breast cancer. Adjuvant treatment for PSCC remains an unresolved issue.
Patient concerns: We reported a case of a 48-year-old postmenopausal female patients with a 2 × 2.5 cm lump presented with no symptoms.
Diagnoses: This patient was diagnosed as PSCC of the breast. The original tumor and first recurrence exhibited triple negative phenotype, whereas the second recurrence was HER2-positive.
Interventions: A tumorectomy with latissimus dorsi flap reconstruction for the second recurrence was performed followed by targeted therapy with trastuzumab.
Outcomes: The patient had a complete remission, which was sustained over the 25 months of follow-up after the tumorectomy.
Lessons: This is the first reported case in literature of a breast PSCC patient with switched immunohistochemical phenotypes during disease recurrence. Surgical resection with flap reconstruction and targeted therapy successfully treated the recurrence.