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. This evidence concerns the gene MUC1 and ampulla of vater adenocarcinoma.