Calcagno was born in Tramontana di Parodi Ligure, in the Province of Alessandria on 3 February 1943.

After studying arts at the diocesan seminary, he attended the Pontifical Gregorian University in Rome, earning a degree in dogmatic theology.

At the national level his assignments included: Secretary of the Italian Priests Commission, Inspector of the Italian Episcopal Conference for Institutes of Religious Sciences, Director of National Missionary Cooperation between Churches, and Treasurer of the Bishops Conference.

He served as Bishop of Savona until Pope Benedict appointed him Secretary of the Administration of the Patrimony of the Apostolic See (APSA) and with the personal title of archbishop on 7 July 2007.

[3] On 20 February 2012 Pope Benedict created him Cardinal-Deacon assigned to the church of Annunciazione della Beata Vergine Maria a Via Ardeatina.