The Argentina forward has 31 goals in La Liga this season after his double for Barcelona against Tenerife on Tuesday, giving him 62 points in the race to be named the continent's leading marksman with two matches still to play.
Udinese's Antonio Di Natale, Chelsea's Didier Drogba and Manchester United's Wayne Rooney, who all have 26 goals and 52 points, have a slim chance of overhauling FIFA World Player of the Year Messi, with two Serie A matches and one Premier League game left.
Gonzalo Higuain has netted 25 for Real Madrid, giving him 50 points, and has three games in which to catch his compatriot as Real have a game in hand over Barca.
Barca coach Pep Guardiola paid tribute to the prolific Messi, still only 22, who has 44 goals in all competitions and needs three more in the league to match the club record of 34 in a season set by Brazilian striker Ronaldo in 1996/97.
"He was chasing passes in second-half added time with the same enthusiasm as if it were the first minute," Guardiola said at a news conference after Barca went four points clear of Real Madrid at the top of La Liga.
"That's because he's a born goalscorer and he has that gift," he added.
Goals scored in Europe's top leagues like the Premier League, La Liga, Serie A and the Bundesliga are awarded two points and those in less prestigious leagues 1.5 points.
Atletico Madrid's Uruguayan striker Diego Forlan won the shoe last season with 32 goals.
