The diagnosis of complete and partial mole with its subsequent risk of trophoblastic malignancy relies on histologic criteria that are sometimes seen in nonmolar conceptuses. We performed karyotypic analysis on 1054 spontaneous abortions during a 43-month period. Villous trophoblastic hyperplasia was graded from 0 to 3 in successfully karyotyped cases of complete mole, triploidy, tetraploidy, monosomy X, trisomy, normal 46,XY, and normal 46,XX without contaminating maternal tissues (n = 649). Parental origin of the extra chromosome was analyzed by polymerase chain reaction in 64 trisomic cases. We also evaluated for each case the developmental stage, presence of uniformly hydropic villi, amnion, villous nucleated red blood cells, and fetal tissue. Villous trophoblastic hyperplasia was increased in spontaneous abortions with abnormal karyotype as a group and in the subgroup with trisomy compared with those of a normal karyotype. Hyperplasia and particularly high-grade hyperplasia (Grades 2-3), equivalent in severity to that seen in proliferative partial and complete moles was most frequent in a subgroup of trisomies involving chromosomes 7 (60% hyperplasia, with 30% of high grade), 15 (50% hyperplasia, 15% high grade), 21 (22% hyperplasia, 11% high grade), and 22 (13% hyperplasia, 4% high grade). Frequency of paternal origin for the extra chromosome in these four trisomies was similar in cases with and without hyperplasia There was a nonsignificant increase in female sex chromosomes with hyperplasia in both trisomic and normal conceptuses. Hyperplasia was more common in trisomic abortions of late stage (> 8.5 wk, P = .013), in those that lacked uniformly hydropic villi (P < .001), and in those that lacked fetal tissue (P = .204). This latter phenotype was particularly common with trisomies 15, 21, and 22.