During the Easter Sunday Mass in 1171 in the small church of Santa Maria in Vado in Ferrara, the celebrant — Father Pietro da Verona, prior of the canons regular — broke the consecrated host at the fraction. From the broken host a jet of blood sprang upward, striking the vault of the apse above the altar and remaining there as a stain that is visible to this day.
Word spread instantly through Ferrara; Bishop Amato of Ferrara examined the relic on the same day. In 1495, Duke Ercole I d'Este had the church expanded into a great basilica around the original chapel; the bloodstained vault was preserved intact within the new structure. Pope Pius IX gave the basilica its current title and elevation; the original vault and the stain remain visible behind glass in a side chapel of the basilica.

