[1] The painting now housed in the church, acquired increasing veneration, such that in 1444 the Gonzaga family from Mantua financed a special tribune.

Though the structure was refurbished in Baroque-style in the seventeenth century, the basic scheme of a domed circular space flanked by altar niches is still evident.

Pilgrims who came to the church to venerate the miraculous painting often left wax votive offerings, many of them life-size models of the donor (sometimes complete with horses).

Pope Alexander VI, in appreciation for the survival of Rome after French occupation, paid homage and gifted a silver effigy to the church.

The Baroque decoration of the church interior was begun in 1644, when Pietro Giambelli frescoed the ceiling with an Assumption as a centerpiece based on designs by Baldassare Franceschini.

The chapel-surrounded tribune or choir, known as the Rotonda, was designed in turn by Michelozzo and Alberti between 1444 and 1476. Notable among the chapels is the fifth (aligned to nave axis), which has a crucifix (1594–8) by Giambologna for his tomb, with statues of the "Active and Contemplative Lives" by his pupil Francavilla, saints and angels by Pietro Tacca,[5] and murals by Bernardino Poccetti.

In the sixth chapel to the left of the nave is a SS Ignatius, Erasmus and Blaise by Raffaellino del Garbo; the next chapel has one of the panels of Annunziata Altarpiece (1507) by Perugino, once at the high altar of the church (the Deposition, begun by Filippino Lippi, is now at the Gallerie dell'Accademia, while other panels are divided between other collections in the world).

The Capella di San Luca, which opens off it, has belonged to the artists confraternity or the Accademia delle Arti del Disegno since 1565.

Many artists are buried in its vault, including Benvenuto Cellini, Pontormo, Franciabigio, Giovanni Angelo Montorsoli and Lorenzo Bartolini.

In 2007, in the west part of the cloister occupied by the Istituto, the group found a monumental stair by Michelozzo, previously hidden, an Annunciation attributed to Paolo Uccello,[citation needed] and some 'Grottesche' frescoes by Morto da Feltre.