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Histologic diagnosis of partial hydatidiform mole (PHM) continues to be problematic, and DNA genotyping has recently become cost-effective for precise separation of PHM from its mimics. We performed a comprehensive reevaluation of histologic parameters of PHM in correlation with DNA genotyping. A total of 143 early abortion specimens were subjected to genotyping as part of the routine workup, resulting in 60 cases of PHM, 52 cases of various chromosomal trisomies, and 31 cases of nonmolar diploid gestations. All available hematoxylin and eosin slides were reviewed retrospectively by 2 gynecologic pathologists blinded to the genotyping results. Significant histologic overlaps were present among genetically confirmed PHM, hydropic abortions, and chromosomal trisomy syndromes. The following morphologic parameters emerged with diagnostic significance for PHM: villus size, presence of 2 villous populations, round or oval pseudoinclusions, at least moderate villous hydrops, cistern formation, and trophoblastic hyperplasia. The most sensitive morphologic features for PHM included villous hydrops (86% sensitivity) or the presence of at least 1 of the following 3 parameters: 2 villous populations, round or oval pseudoinclusions, and cisterns (84% sensitivity). The presence of cisterns and villous size ≥2.5 mm had the highest positive predictive value (90%) for PHM. In conclusion, no single or combined morphologic features are sufficient for definitive diagnosis of PHM. The presence of any one of the following histologic findings should prompt DNA genotyping workup to rule out PHM: round or oval pseudoincludions, cistern formation, 2 populations of villi, and a villous size of ≥2.5 mm.