The year 1546 did not begin auspiciously. Michelangelo, now seventy-one years old, had been deathly ill for the second time in a little more than a year. That winter, a fire had damaged the roof of the Pauline Chapel thereby exposing Michelangelo's partially completed frescoes to the elements. Since it was cold and damp, the artist was not currently working in the chapel, but he worried about the building's neglect. The looming, incomplete hulk of new St. Peter's sucked all his attention and resources.

After more than thirty years of building destruction and construction, St. Peter's was a depressing sight. Vaults linked the four massive piers, but the central crossing was still open to the sky; the high altar and the grave of Saint Peter were protected from the elements by a temporary structure. Broken pieces of the nave columns and entablature lay where they had been pulled down in ruinous haste. The old building was left to deteriorate; the new structure was covered with scaffolding, festooned with ropes, cranes, and hoists, and surrounded by mud, disordered piles of stone, and the foul stench of animal droppings. From near or far, St. Peter's looked more like a Roman ruin than a new church.

The building was granted a reprieve from further indignity when Antonio da Sangallo the Younger died in September 1546. The death of the pope's prolific architect left many Roman building projects incomplete, most notably St. Peter's and the Farnese Palace.