In breast cancer, aggressive tumor biology and the corresponding poor prognosis is associated with amplification or overexpression of the human epidermal growth factor receptor 2 (HER2). Trastuzumab has significantly changed the natural history of HER2-positive breast cancer. However, resistance to trastuzumab remains a substantial clinical problem. Ado-trastuzumab emtansine (T-DM1), an antibody-drug conjugate, has demonstrated impressive results in second- or later-line treatment of HER2-positive breast cancer. We report a case of 43-year-old female with previously trastuzumab-treated HER2-positive breast cancer relapsed with pulmonary lymphangitis carcinomatosis that responded dramatically to T-DM1 therapy.