Metaplastic squamous cell carcinoma of the breast is a very rare form of breast cancer that consists of both glandular and nonglandular components mixed with epithelial and mesenchymal tissues. Worldwide, the incidence of this tumor is between 0.1 and 2%. Because of the rarity of this tumor and heterogeneous behavior of the tumor cells, it is difficult to establish the standard therapeutic approach. We report 2 cases of metaplastic squamous cell carcinoma of the breast in young patients with different responses to treatment strategies. The first case is a premenopausal female with metaplastic squamous cell carcinoma treated with surgery, chemotherapy, and radiotherapy, and the second case is perimenopausal metaplastic squamous cell carcinoma with sarcomatoid subtype and osteoid matrix production which progressed on chemotherapy and was treated with surgery and radiation.