Our Lady of the Sign Church is an Orthodox church in the Žvėrynas district of Vilnius, built in 1903.

The idea of building a new Orthodox church in Vilnius came from Orthodox Brotherhood of the Holy Spirit, which also organised a collection of funds in the whole Russian Empire. The church, constructed in the most popular Neo-Byzantine style, was consecrated in 1903 by Iuvenaliy, the Orthodox archbishop of Vilnius. He also opened a school for poor children and a library which were to be run by the church's clergy. In order to conmemorate the day, he granted to the newly established parish a copy of Our Lady of Kursk icon.

Unlike many other Orthodox churches in Vilnius, the church was not closed during the World War I, nor the World War II. The Soviet government agreed to register it as a parish church in 1948. Before 1956, the church was robbed a few times, losing part of the icons from the original iconostasis which had to be replaced by a far humbler one. The church was fully restored inside and outside in 2009.