High above the baldacchino and the altar rises the dome designed by Michelangelo, built with the same double shell as Brunelleschi's earlier one in Florence, but designed more spherically, like the Pantheon. Out of reverence for that ancient architectural wonder, Michelangelo is said to have made this cupola a meter shorter in diameter than the Pantheon's, but the measurements of the dome are still eye-popping. The highest point towers 120m above the floor and the diameter of the dome measures in at 42.3m. At the time of Michelangelo's death in 1564, only the drum of the dome had been completed. Work remained at a standstill until 1588, when 800 laborers were hired to complete it. Toiling round the clock, they finished the dome on May 21, 1590.

Around the bottom of the drum, the key biblical passage of the basilica is inscribed: "You are Peter, and upon this rock I will build my church; I will give you the keys to heaven." As the scriptural justification for the opulence that is St. Peter's, references to these lines abound throughout the rest of the Vatican, especially in the Sistine Chapel. Representations of Mary, Christ, and the Evangelists adorn one level of the dome, choirs of angels fill up four more levels, and God presides on high.