The imperial basilica of San Vitale al Quirinale, built under the pontificate of Pope Siricius after 386 and consecrated and richly decorated by Pope Innocent in 402 (Luigi Hutter and Vincenzo Golzino) is the first public Christian basilica with a baptistery (still not found) not founded on pre-existing pagan temples, mentioned in the Liber pontificalis, built by the Emperor Theodosius at the behest of Saint Ambrose of Milan, in honor of the miraculous discovery of the bodies of martyrs Gervasius and Protasius in Milan.

[3] San Vitale was restored several times, most importantly when it was extensively rebuilt by Pope Sixtus IV before the Jubilee of 1475.

The apse, a surviving part of the original 5th century church, is decorated with a fresco by Andrea Commodi, The Ascent to Calvary.

Among the cardinals who previously took their title from the church were: John Fisher, executed for treason in 1535 by Henry VIII of England; and Giovanni Maria Ciocchi del Monte, who became Pope Julius III (1550–1555).

[8] The titulus was restored by Pope Leo XIII in 1880, with the appointment of Cardinal Andon Bedros IX Hassoun.