The institute was founded in 1878, under the name of Regio Liceo Ginnasio, by Francesco De Sanctis, at the time Minister of Public Education. It is located on the premises of the Jesuit College, built in 1574 by Bartolomeo Ammannati and acquired in 1775 by the Piarist Fathers. In the late 19th century the acquisition of scientific instruments began; some of the equipment was constructed in the school.

The collection of instruments for Physics (19th and 20th centuries) includes instruments for Optics and Acoustics, electrical machines and other devices. The naturalist collection, formed for educational purposes in the late 19th and early 20th centuries, consists of over 400 specimens. Both the instruments and the specimens are still today utilised in the school’s laboratories of Physics and Science.