The skyline of Florence is dominated by a single building, the Basilica di Santa Maria del Fiore, or simply the Duomo. Though the tower of the Palazzo Vecchio vies with it for height, it is still dwarfed by the sheer volume of the cathedral's dome.
Built by Filippo Brunelleschi and inspired by the Pantheon in Rome, the dome was the first of such magnitude to be attempted since antiquity. It was completed in 1436 and remains the largest masonry dome ever built. (By contrast, the Pantheon was built in concrete, but this technique had been lost since Roman times.)
For more history and photos, see Brunelleschi's Dome.