Pathologic and immunohistochemical studies of 13 patients with mucinous cystic neoplasm of the pancreas were performed in order to determine whether these lesions represent overt or latent malignancy. In 9 patients with mucinous cyst-adenoma, the foci of mucus-rich columnar epithelia formed the usual pattern of stratifications and papillary projections with a benign appearance and did not stain with mouse monoclonal antibody to CEA (CM-010, Mochida, Japan). In contrast, the foci of mucus-poor columnar epithelia which were in a focal distribution showed moderate to severe atypical hyperplasia and reacted strongly with anti-CEA in 6 of the 9 patients. In addition, areas of both noninvasive and invasive mucinous cystadenocarcinomas in 4 patients, which were composed primarily of mucus-poor columnar epithelia, showed diffuse cytoplasmic and/or apical reactivity with anti-CEA. Based on these results, we conclude that severe atypical epithelial hyperplasia composed primarily of mucus-poor columnar epithelia represents a precursor to mucinous cystadenocarcinoma, and, therefore, mucus-poor atypical epithelia may undergo malignant transformation.