The authors have previously shown that duodenal adenomas in familial adenomatous polyposis (FAP) patients typically reveal abundant cells with endocrine differentiation (ED), Paneth differentiation (PD), and goblet cell differentiation (GD). However, the biological significance and proliferative potential of these cells is unknown. To study the proliferative properties of cells with ED, PD, or GD in FAP-associated duodenal adenomas, the authors used a double-labeling immunohistochemical technique to detect simultaneously the presence of proliferating cell nuclear antigen (PCNA), and either chromogranin or lysozyme in individual neoplastic cells. Adenomatous cells with GD were identified morphologically and also evaluated for the degree of PCNA expression by immunohistochemistry. Duodenal adenomas and the adjacent nonadenomatous epithelium from 10 FAP patients were studied. Cells with ED, PD, and GD were present in all adenomas, and constituted 14.1%, 11.6%, and 17.7% of adenomatous cells, respectively. The overall proliferative index of nondifferentiated adenomatous cells was 33.3%, which was similar to the proliferative index obtained for adenomatous cells with GD (31.2%) and nonadenomatous crypt goblet cells (34.9%). In contrast, adenomatous cells with ED and PD showed a significant decrease in their proliferative potential (P < .001). Only 6.0% and 7.3% of cells with ED and PD, respectively, were proliferative. Nonadenomatous crypt endocrine and Paneth cells showed no proliferative potential (proliferative index 0%). These results suggest that, in the process of proliferation and differentiation, specific subpopulations of adenomatous cells attempt to recapitulate the biological characteristics of their normal counterparts in the small intestinal crypts. Adenomatous cells with ED and PD are hypoproliferative, a finding that is consistent with their differentiated phenotype and suggests that these cells may not participate as actively in the growth of these lesions.