Primary squamous cell carcinoma (SCC) of the breast is a rare malignancy whose optimal treatment and prognosis are unknown. A patient with SCC whose tumor responded dramatically to chemotherapy as part of multimodal treatment is presented. A 61-year-old woman had a palpable 5.5-cm tender left breast mass with overlying skin edema and erythema and irregular margins by mammography. Fine needle aspiration revealed malignant squamous cells with keratinization; incisional biopsy confirmed SCC. Extensive evaluation for an extramammary primary site of disease was negative. Neoadjuvant cisplatinum and 5-fluorouracil (5-FU) led to tumor shrinkage and complete resolution of pain and erythema. Modified radical mastectomy with post-operative chest wall radiation were performed. Neither residual invasive carcinoma nor metastatic nodal disease was found, though intraductal carcinoma with marked squamous features was identified. The patient remains disease-free 2.5 years after diagnosis. Cisplatinum-based chemotherapy should be considered in the treatment regimen of this disease.