[1] De Paolis was born in 1935 in Sonnino, Latina, and took his final vows as a member of the Missionaries of St. Charles Borromeo (Scalabrinians) on 4 October 1958.

[2] On 30 December 2003, De Paolis was appointed Secretary of the Apostolic Signatura and Titular Bishop of Thelepte by Pope John Paul II.

[2] He received his episcopal consecration on 21 February 2004 from Cardinal Angelo Sodano, with Archbishop Silvano Maria Tomasi, CS, and Bishop Francesco Saverio Salerno serving as co-consecrators.

"[6] De Paolis was named President of the Prefecture for the Economic Affairs of the Holy See by Pope Benedict XVI on 12 April 2008, also being promoted to Titular Archbishop of Thelepte.

"[8] On 25 January 2010 he was appointed a member of the Apostolic Signatura, the Church's highest court, in addition to his duties at the Prefecture for the Economic Affairs of the Holy See.

He was created Cardinal-Deacon with the title of Gesù Buon Pastore alla Montagnola by Pope Benedict XVI in the consistory of 20 November 2010.

[13] On 20 October 2011, de Paolis disclosed, in a letter,[14] that an investigation of Regnum Christi uncovered concerns that would require rewriting the group's norms.

De Paolis said in an interview that Pope Benedict tasked him only with guiding the Legion and helping rewrite its norms – not "decapitating" its leadership or avenging wrongdoing.

Reports estimate 70 of the 890 Legion priests and upwards of a third of the movement's 900 consecrated women have left or are taking time away to ponder their future.

[19] In October 2012, de Paolis told the Italian newspaper La Repubblica that there was precedent for the Pope to pardon Paolo Gabriele, who had been found guilty of stealing confidential papal documents and leaking them to the media.