Sixty molar and nonmolar placentas with hydropic features [23 complete moles, 14 partial moles, 8 moles-not further classified, and 15 hydropic, nonmolar placentas] were evaluated immunohistochemically for expression of Ki-67, proliferating cell nuclear antigen (PCNA), and p53, and the results were compared with DNA ploidy and S-phase fractions derived from flow cytometric analysis. The data were evaluated to determine if proliferation marker staining could aid in distinguishing mole from non-mole and partial from complete mole. PCNA and p53 expression did not discriminate between moles and non-moles. However, the percentage of rimming villous cytotrophoblast nuclei reactive for Ki-67 differed significantly between moles and non-moles (p < 0.001). All molar specimens contained at least one medium-sized villus with > 70% Ki-67-positive cells, whereas the maximum percentage of reactive cells in hydropic abortuses was 22%. These results suggest that percentage Ki-67 positivity in rimming cytotrophoblast nuclei may aid in distinguishing a mole from a nonmolar, hydropic abortion.