We describe a case of neonatal periventricular leukomalacia (PVL) without evidence of twin-to-twin transfusion syndrome (TTTS) following discordance in nuchal translucency (NT). A 34-year-old woman with monochorionic twins after in-vitro fertilization and embryo transfer was referred to our hospital. At gestational week 11, fetus A showed increased NT (7.0 mm) and normal crown-rump length (CRL) (34.3 mm). Fetus B had normal values, with a NT of 1.3 mm and a CRL of 32.3 mm. Both twins maintained growth throughout pregnancy, with no evidence of TTTS. During the antepartum period, daily fetal heart rate monitoring showed a reassuring pattern. Cesarean delivery was performed in gestational week 32. Neonates A and B weighed 2,071 and 1,617 g, respectively (discordancy rate 21.9%), each with an Apgar score of 8 at 1 min. Soon after birth, brain ultrasonography of neonate A revealed high-echoic periventricular lesions bilaterally, and brain magnetic resonance imaging on day 7 revealed PVL. Neonate B showed completely unremarkable results.