Mucinous cystic tumors of the pancreas must be distinguished from other cystic lesions because of their potential malignancy. Our purpose was to assess the reliability of gastric M1 mucin analysis in the fluid of cystic lesions of the pancreas in comparison or association with carcinoembryonic antigen. M1 mucin and carcinoembryonic antigen were measured in cyst fluid obtained preoperatively by fine-needle aspiration. The lesions consisted of 12 serous cystadenomas, 9 mucinous cystadenomas, 8 cystadenocarcinomas and 6 intraductal mucinous hypersecreting neoplasms. Thirty pancreatic pseudocysts complicating well-documented chronic pancreatitis were also examined. In addition, M1 mucins were localized by immunoperoxidase staining in fetal and normal adult pancreas and in mucinous and serous tumors. Carcinoembryonic values of > 20 ng/ml and M1 mucin values of > 50 U M1/ml represented 82 and 78% sensitivity, respectively, as well as 100% specificity for distinguishing mucinous lesions from serous cystadenomas; the sensitivity for this purpose was 100% using these criteria in combination. Carcinoembryonic antigen values of > 300 ng/ml and M1 mucin values of > 1,200 U M1/ml represented 56 and 30% sensitivity, respectively, as well as 100% specificity for distinguishing mucinous lesions from pseudocysts; the sensitivity for this purpose was 60% using these criteria in combination. By immunohistology, M1 mucins were detected in the wall of mucinous lesions but not in fetal and normal adult pancreas and in serous cystadenomas. Measurement of M1 mucin antigen in cyst fluid could thus improve the diagnosis of mucinous cystic lesions of the pancreas.