The 31-year-old Garmin rider snatched the pink jersey from Spain's Joaquim Rodriguez on the final time trial stage in Milan, forging a winning margin of just 16 seconds after 21 stages.
Last year's winner Cristiano Ronaldo came second, with Messi's teammates from Barcelona's historic 2008-09 treble-winning side -- Spain midfielders Xavi and Andres Iniesta plus Cameroon striker Samuel Eto'o (now at Inter Milan) -- rounding out the top five.
This preseason, the NBA is hosting NBA Europe Live presented by BBVA, during which the Boston Celtics will play Fenerbahce Ulker in Istanbul, Turkey and EA7 Emporio Armani in Milan, Italy and the Dallas Mavericks will play Alba Berlin in Berlin, Germany and FC Barcelona in Barcelona, Spain.