Lorenzo Zanetti competed in the 125cc Italian Championship in 2004 and clinched the Honda Trophy before having the opportunity to compete in eight Grands Prix that year. The rider from Brescia earned a full-time ride for 2005 on the Skilled Racing Team Aprilia and finished 17th overall with a best placing finish of fifth at Brno. A quiet 2006 saw him conclude the World Championship in 21st position.

In 2007 he represented Team Sicilia, once again onboard an Aprilia, and was ranked 19th at the end of the season. The Italian undertook a new challenge alongside Tomoyoshi Koyama as a KTM satellite rider in 2008 but slipped down to 22nd in the final standings. In 2009, Zanetti’s fifth full season in Grand Prix competition, he rides for the Ongetta ISPA team.