Despite being born in Naples, Antonio Di Natale made the move north for his footballing career, joining Empoli’s youth system. While at Empoli, he was loaned out three times, enjoying success with Viareggio in the 1998–99 campaign, where he scored 12 goals in 25 games for the Tuscan side. Upon his return to his parent club, he finally made his breakthrough into the first team squad and established himself as an integral member of the side. He netted six times in 25 appearances for Empoli during the 1999–2000 campaign, as Empoli finished in ninth place in Serie B. Empoli won promotion to the Serie A in 2002 after finishing in fourth place during the 2001–02 Serie B season with 67 points. They finished with 60 goals, the largest tally in the competition, and Di Natale finished as the club’s top goalscorer with 16 league goals. In Empoli’s first season back in the topflight, he helped the club fight off relegation by netting 13 times in the league. This included a hat-trick in Empoli’s 4–2 defeat of Reggina on 17 November 2002. The next season was less fortunate for Di Natale, who only scored five goals in the league. Following two seasons in the Serie A, Empoli were relegated back to the Serie B at the end of the 2003–04campaign.