Named Guilio Pippi, but called Romano after his native city, he trained under and was one of the most prized pupils of the great Renaissance master Raphael. Raphael, busy with his many commissions and official posts, often employed many of his students to help in his undertakings. Romano and other students were often asked to aid Raphael in the prepatory work of his major commissions, executing trial scale models of pictures from Raphael's sketches or verbal directions. Romano would draw the cartoons (a term referring to a full scale prepatory drawing on sheets of heavy paper or light cardboard) and Raphael would then come and add paint to them. While more then half of the surface of Raphael's most important commission's were done by his own hands most of the detailed studies were executed by Romano.

When Raphael contracted a serious illness and died at the young age of 37, Romano helped to complete many of the master's unfinished works.

Romano would establish a reputation as a fine artist after the death of Raphael. His masterpiece was the building and designing of the Palazzo Te in Mantua for Duke Ferderigo Gonzaga. Romano not only designed the exterior but also the interior of the building. It is decorated with frescoes, the most impressive being those in the room of the Giants. There his "Polyphemus" is found as well as a host of other Titans and Giants who are depicted after their fateful battle with the Olympians.