As a cardinal he visited the city in 1452 and understood it as a total artwork offering a synthesis of the arts. In fact, he was the first to write a laudation on Nuremberg.

In enthusiastic words de described: When one comes from Lower Franconia and catches sight of the City from afar it reveals its majestic splendor, which is highlighted by the beauty of its churches and the broadness of its streets. The Imperial Castle proudly overlooks the City, the townhouses seem to have been built for princes.“ (quoted according. to Wilhelm Schwemmer: Architektur und Plastik in „Nürnberg, Geschichte einer europäischen Stadt“, 1982).

Piccolomini was elected Pope Pius II in1458. He died in 1464. His tomb is in the Church Sant´Andrea della Valle in Rome.

He had an especially close relationship with the Holy Roman Empire of the German Nation and was an admirer of the Central European Culture.