Ado-trastuzumab emtansine (T-DM1) is a novel antibody–drug conjugate with current FDA recommendation for second-line treatment of HER-2-positive metastatic breast cancer. It is a human epidermal growth factor receptor (HER-2)-targeted antibody–drug conjugate composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent DM1 (derivative of maytansine). Ado-trastuzumab emtansine improved both progression-free and overall survival as reported in EMILIA trial. With ongoing clinical trials in adjuvant and first-line setting for HER-2-positive early and metastatic breast cancer, it is prudent to recognize, report, and treat any adverse events related to T-DM1. We report a case of acute pancreatitis in a 54-year-old woman with metastatic breast cancer after she received her first dose of ado-trastuzumab emtansine. To the best of our knowledge, this is the first reported case of acute pancreatitis with probable association with ado-trastuzumab emtansine.