The church stands at the crossroads between Italy and Switzerland, in the place where the Virgin appeared back in 1504. 

According to tradition, at dawn on 29 September 1504, the Virgin appeared to Tirano resident Mario Omodei, promising that the plague would end if a church were built in her honour in the exact place where she appeared, meaning near the bridge over the Folla and outside of the town walls. Comforted by a series of events that were believed to miracles, the residents acted quickly and on 25 March 1505, during a solemn ceremony, the first stone of the building was laid at the foot of the medieval Church of Santa Perpetua.

Featuring a nave and two side aisles and a Latin-cross floor plan, the basilica is the most beautiful Renaissance building in Valtellina. The church has an exuberance of stucco decorations and sculptures and the interior still contains a colossal organ with exquisite carving that was begun in 1608 by Giuseppe Bulgarini from Brescia and completed in 1638 by G.B. Salmoiraghi from Milan. Thanks to its location, it has always drawn the faithful from throughout Europe. In 1946, Pope Pius XII proclaimed the Blessed Virgin of Tirano "special heavenly patron of all of Valtellina".