Multifocal chorangiomatosis (MC) is an uncommon villous capillary lesion sharing some features with villous chorangiosis and placental chorangioma. We prospectively identified 53 cases of MC among 5429 consecutively accessioned placentas of >20 weeks gestation over a 10-year period. Two gestational age (GA)-matched controls were selected for each case from the same cohort and a case control analysis of associated clinical and pathologic features was performed. Multifocal chorangiomatosis was seen at all GAs but was most frequent in very preterm placentas (<32 weeks). Avascular villi, villous chorangiosis, and distal villous immaturity were each seen in approximately half of placentas with MC. Other common placental findings included concentric narrowing of fetal villous arterioles, villous edema, and dysmorphic villi. Only one case had an associated placental chorangioma. Maternal factors significantly associated with MC were advanced maternal age, non-African-American ancestry, nonprimigravid status, and >5 previous pregnancies. Infants with placental MC had a significantly increased prevalence of congenital anomalies. Multifocal chorangiomatosis was subcategorized as extensive versus patchy based on the size of the largest focus (> versus < ×2 microscopic field). Fetuses with extensive MC, when compared with patchy MC, were more likely to have congenital anomalies and stillbirth and to be large for GA. Paradoxically, those with patchy MC were more likely to be small for GA. The results of this study suggest that MC may represent an abnormal proliferation of the paravascular capillary net in proximal villi related to fetoplacental developmental anomalies and abnormal fetal blood flow.