To assess the incidence, diagnosis, pathogenesis, and clinical and placental associations of congenital cytomegalovirus infection, 34 cases thereof diagnosed by placental/fetal or neonatal workup (group 1), and 494 placentas with villitis of unknown etiology (group 2) were extracted from a 6083-case placental database. 28 clinical and 47 placental phenotypes were compared between the two groups by Yates 2 or ANOVA using the Bonferroni correction. 26 group 1 cases did and 8 did not feature placental villitis, but all cases were positive as shown by immunohistochemistry and/or in situ hybridization. Only 5 differences were statistically significant (p Bonferroni < 0.0056): gestational age 29.8 ±6.5 vs. 35.5 ±4.9 weeks, perinatal mortality 67.6 vs. 16.2%, nonmacerated stillbirth 20.6 vs. 3.0%, macerated stillbirth 38.2 vs. 9.3%, and diffuse villous fibrosis 44.1 vs. 12.5%, between group 1 and group 2, respectively. The absence of significant differences in placental phenotypes between group 1 and group 2 other than the histological pattern of villitis indicates that not the cytomegalovirus villitis but the direct viral cytopathogenic effect on fetal organs makes the difference in the dire clinical outcome in the former. As about a third of cytomegalovirus infections show no villitis, the combination of the clinical picture and placental patterns creates the best chance to detect congenital cytomegalovirus infection.