Whilst at Vicenza, Pistone caught the eye of Roy Hodgson, who was manager of Internazionale at that time.

Pistone transferred to Internazionale for the 1996–97 season, fulfilling a childhood ambition by signing for his home town club.

After an impressive single season at Internazionale, Newcastle United manager Kenny Dalglish signed Pistone for a fee of £4.5 million in July 1997.

Despite primarily being a full-back, Pistone made his debut against Sheffield Wednesday as a central defender (a position which he appeared in on a number of occasions in his first season with the Magpies).

Pistone was not allocated a squad number and was forced to train with the reserve team, along with former club captain Rob Lee.

However, he only managed to feature in 3 games before suffering a cruciate knee ligament injury, ending his season prematurely.

After impressing manager Geo Van Pyperzeele, Pistone signed for the club on 6 December 2007 until the end of the season, and was given the number 4 jersey.

As part of the Italian Under-21 national team, Pistone won the European Under-21 Championships in 1996, taking and scoring Italy's second penalty in an eventual 4–2 shoot-out victory in the final against Spain, following a 1–1 draw.

Since retiring from football, Pistone has made a number of appearances on the Italian Poker Circuit, and participated in the eight Annual Night of Aces event in 2010.

Pistone also owns and runs a restaurant in Milano near Central Station, Italy, which specialises in Saveloy Dip.