Background: Intraoperative frozen section analysis is frequently used to obtain a histological diagnosis at the time of resection and to assess resection margins. Although many surgeons perceive a clinical benefit, particularly with respect to the transected resection margins, the limitations and pitfalls of frozen section analysis have not been well documented. Case: Here, we report a case of serous cystadenoma with background pancreatitis masquerading on frozen section as an invasive pancreatic ductal adenocarcinoma. This interpretation was a surprise in light of preoperative imaging that was highly suggestive of a benign cystic tumor, but nevertheless prompted intraoperative consideration of a more radical operation to ensure a complete resection was achieved. Conclusions: Frozen section analysis is an imperfect test, and misdiagnoses can potentially impact patient outcomes adversely. Intraoperative decisions must carefully integrate the preliminary pathological interpretation with the overall clinical context. Further studies are warranted to more fully characterize the accuracy, utility, and cost-effectiveness of intraoperative frozen section analysis for pancreatic surgery.