Background: Cases of differential congenital cytomegalovirus (CMV) infection in twins are rarely reported. The chance of congenital infection and the clinical outcome of monochorionic diamniotic or dichorionic diamniotic twins are highly uncertain. Cases presentation: We reported a case of differential congenital CMV infection in dichorionic diamniotic twins. Despite being exposed to the same maternal environment and similar genetic background, twins reacted differently to maternal infection and presented with non-concordant infection status. The potential mechanism of discordant infection from aspects of type of chorion and placenta and immune status has been discussed through literature review. Conclusion: CMV infection can present as differential congenital infection in twin pregnancy, with various clinical symptoms. Fetal cellular immune function may be involved in the pathogenesis.