The separation of complete from partial hydatidiform mole and of partial mole from placentas with hydropic change on gross and microscopic evaluation can be difficult, and ploidy provides important diagnostic information. We applied an immunohistochemical marker of proliferation, Ki-67 (MIB-1), to 10 complete moles, 11 partial moles, and 8 placentas with hydropic change to determine whether growth fraction differs in these three placentas and can aid in diagnosis. Ploidy was confirmed using flow cytometry and fluorescence in situ hybridization with probes to chromosomes 7 and 2. The Ki-67-determined growth fractions (number of positive cells/total number of cells) for villous stromal cells, cytotrophoblast, and proliferating trophoblast were evaluated separately by counting 200 cells of each population. Growth fraction on stroma did not differ among the three entities. Mean percent growth fraction for cytotrophoblast was 13.3% for hydropic change, 14.6% in partial moles and 38.7% in complete moles (P = .004 hydropic change to complete moles, P = .003 partial moles to complete moles). There was no significant difference between hydropic change and partial mole. Mean percent growth fraction for proliferating trophoblast was 38.5% in hydropic change, 25.9% in partial moles, and 67.1% in complete moles (P = .08 hydropic change to complete moles, P = .004 partial moles to complete moles). Again, no significant difference was identified between hydropic change and partial moles. Ploidy analysis using fluorescence in situ hybridization and flow cytometry confirmed diploidy in hydropic change and complete moles and triploidy in partial moles. Ki-67 may be useful in separating complete moles from partial moles but not partial moles from hydropic change.