The building was erected in 1574 by Bernardo Buontalenti for Grand Duke Francesco I de’ Medici on an area at that time near the countryside, inside the Medici gardens. Designed as a laboratory for scientific experimentation, in 1588 it became the seat of the Opificio delle Pietre Dure. On the death of Grand Duke Francesco I, in 1587 the palazzo was inherited by don Antonio de’ Medici who took up residence here in 1597, commissioning numerous works to embellish the rooms and garden which hosted sculptural groups by Giambologna.

Inside the palazzo, don Antonio created a perfect research laboratory, known as the Fonderia, that became a veritable centre of experimentation, assembled various scholars interested in chemical analyses, and even installed a rich chemistry-alchemy library containing several handwritten prescription pads, today conserved in the Biblioteca Nazionale Centrale di Firenze (BNCF).

It is currently the headquarters of the Court of Assizes and Appeal, and no testimony remains of the scientific activity that was conducted there in the course of its history.