Abstract Radical pancreatoduodenectomy for treatment of pancreatic carcinoma has been the surgical standard of care for the past four decades. The recent popularization of pylorus-sparing pancreatoduodenectomy to treat benign pancreatic disease, because of its decreased morbidity and long-term nutritional consequences, has led to the use of this procedure in cases of pancreatic carcinoma. We report recent experience with three patients with pancreatic carcinoma in whom pyloric preservation would have compromised the potential chance for curative resection or compromised palliation because of occult spread of tumor to a region not resected with this new operative approach. Two patients had proximal, microscopic intramural spread of pancreatic adenocarcinoma within the duodenum or antrum—a mode of spread not previously reported with pancreatic carcinoma. Both patients had no other evidence of metastatic involvement, and both would have had positive surgical margins in a pylorus-sparing pancreatoduodenectomy. A third case demonstrates a true submucosal recurrence of pancreatic carcinoma after a pylorus-sparing pancreatoduodenectomy. It is debatable that any case demonstrating intramural spread within the duodenum could be cured with a standard Whipple resection as this may well represent another sign of incurability, like lymphatic or perineural spread, but it is clearly a major potential obstacle to palliation if submucosal recurrences occur as a result of the use of the pylorus-sparing pancreatoduodenectomy in cases of pancreatic cancer. The use of pylorus-sparing pancreatoduodenectomy in resectable pancreatic cancers must be viewed skeptically at this time.