A painter, like his brothers David and Benedetto, he was the master of Michelangelo. His son Ridolfo was to be a disciple of Fra Bartolomeo.
He is considered to be, like Leonardo, one of Verrocchio's pupils. To him were once attributed two masterpieces, the Annunciation in the Uffizi, today attributed by most critics to Leonardo, and a singular painting, the Miller Tondo in Palazzo Vecchio, coming from the circle of Verrocchio, Leonardo and Cosimo Rosselli.
In Florence his major works are found in the churches of Santa Trinita and Santa Maria Novella; in the latter church, in the Portrait of a Lady in the Tornabuoni Chapel, painted prior to 1490, he foreshadows the dynamic pose of the Mona Lisa. Other masterpieces by him are found in the Uffizi Gallery (such as the Adoration and the Portrait of Giovanna Tornabuoni) and in Palazzo Vecchio (Allegory of Florence). Noteworthy are his Last Suppers in the Refectory of Ognissanti and the San Marco Monastery (another of his Last Suppers is found in the Badia a Passignano). Nor should we forget the Episodes from the life of Santa Fina in the Collegiate of San Gimignano.
In January 1504 he too was, with Leonardo, one of the experts consulted on where to place Michelangelo's David.