He had strong connections with the House of Medici, being the brother of Lucrezia Tornabuoni, and therefore Lorenzo il Magnifico's uncle.

[2] In 1443 was named director of the branch in Rome, being Leonardo Vernacci the predecessor,[3] as treasurer of Pope Sixtus IV.

[4] Around 1475, Giovanni Tornabuoni commissioned a portrait of his sister by Domenico Ghirlandaio, which is now in the National Gallery of Art in Washington, D.C.[5] He was also Florentine ambassador in the Papal court in 1480 and 1484, and gonfaloniere di Giustizia in 1482.

In 1485 he signed a contract with painter Domenico Ghirlandaio for a grand cycle of frescoes in what was to become the Tornabuoni Chapel in the church of Santa Maria Novella in Florence.

[9] Piero had no talent for running the bank and depended on his secretary and his great-uncle Giovanni Tornabuoni to handle everything.