The Liquigas rider held off the challenge of two-time champion Gilberto Simoni at the end of the 163km 12th stage which incoporated the Colle dell'Agnello - the highest climb of this year's race - and the first category Col d'Izoard.

Di Luca now leads by 63 seconds overall from his Italian compatriot Marzio Bruseghin of the Lampre team.

Andrea Noe', who started the stage in the maglia rosa, lost several minutes on the first major mountain stage of the race, while the highly touted pair of Yaroslav Popovych and Paolo Savoldelli also saw their GC ambitions disappear.

Christophe Riblon (AG2r Prévoyance) and Yoann Le Boulanger (Bouygues Telecom) launched an early attack and built up a lead of over 17 minutes.

But the real action was happening behind as an elite group of ten formed on the 21.3km Hors Cat ascent of the Colle dell'Agnello which peaked at 2744m.

Le Boulanger took the Fausto Coppi prize at the summit with 60km remaining with a group consisting of Di Luca, Simoni, Andy Schleck, Damiano Cunego, Eddy Mazzoleni and Leonardo Piepoli just under six minutes behind with Riblon sandwiched inbetween.

Le Boulanger had been caught by the time the riders crossed the Col d'Izoard with 21km left although Di Luca's attack over the final stages of the climb was stymied on the long descent towards the finish.

Simoni's Saunier Duval team-mate Piepoli fell out of the lead group on that climb after setting the tempo for long periods and the remaining five riders went under the kilometre to go banner together.

Di Luca attacked first but Schleck followed as the gradient climbed to 14%.

Simoni bridged the gap on the cobbled climb and went past the rider from Luxembourg but the Liquigas man held on for his second stage victory of this year's race with Schleck seven seconds back in third followed by Mazzoleni and Cunego.

Entering Friday's 13-km mountain time trial, Schleck is fourth on GC at 1:25 with Cunego sixth at 2:10 and Simoni in eighth at 2:34.