Herein, we report 2 cases of ampullary adenocarcinoma and 1 case of duodenal adenocarcinoma with positive IHC tumor staining for CK7 or MUC1 that failed 2 lines of prior chemotherapy with oxaliplatin, irinotecan, and 5FU but successfully achieved durable and exceptional responses to nab‐paclitaxel and gemcitabine with or without cisplatin combinations. The gene discussed is KRT7; the disease is duodenal adenocarcinoma.