Chronic villitis of unknown etiology (CVUE) is a frequently encountered placental lesion associated with poor pregnancy outcome. We examined 22 twin placentas with CVUE to determine its distribution and clinicopathological significance in twin gestations. CVUE affected both twins' placental portions with an approximately equal degree of severity in 12 of 22 cases (9 dichorionic, 3 monochorionic). Only one twin's placental portion was affected in 8 cases (8 dichorionic). In the remaining 2 (1 dichorionic, 1 monochorionic), both placental portions were affected, but the CVUE was significantly more severe in one. The CVUE varied in extent from rare foci to diffuse involvement. Seven of the 22 (32%) pairs of twins had intrapair weight differences of 15% or greater, and 14 pairs were premature. The twins with placental involvement by CVUE had a lower mean birthweight than their cotwins with less or no CVUE; however, these results were not statistically significant. CVUE may affect placentas from one or both twins, and may be a cause of discordant twin size.