Flyhalf Andrea Scanavacca was the surprise omission from Italy's 41-man preliminary World Cup squad, which was announced on Monday.
The Cammi Calvisano player was one of the heroes of the two-win 2007 Six Nations campaign, the Azzurri's most successful ever.
The 33-year-old scored 22 points in the historic 17-37 victory over Scotland in Edinburgh in February, Italy's first away win in the tournament.
Scanavacca is also the all-time top-scorer in the Italian domestic championship.
Coach Pierre Berbizier's decision to leave him out means Argentine-born flyhalf Ramiro Pez looks certain to be Italy's playmaker at the World Cup in France this autumn.
Pez, who plays for French club Bayonne, is capable of flashes of brilliance, but has often been criticised for inconsistency.
Scanavacca's Calvisano team-mate Roland De Marigny will probably be Pez's back-up.
De Marigny usually plays full-back.
The squad features two uncapped players who have been bumped up from the Italian Under-21 set-up.
They are Rolly Gran Parma flanker Paul Derbyshire and Benetton Treviso back Alberto Sgarbi.
It also includes Fijian-born Overmach Cariparma Number 8 Manoa Vosavai, who will become eligible to play for Italy on September 2, five days before the World Cup kicks off.
"This selection is the start of our World Cup adventure," Berbizier told the Italian Rugby Federation's website.
"It is a list that brings together many experienced players with interesting youngsters like Derbyshire and Sgarbi.
"At the start of July we'll start work at a camp in Valle d'Aosta. A great deal of attention will be devoted to fitness in the initial period.
"Then as we get closer to our World Cup warm-up matches against Japan and Ireland we'll concentrate more and more on our style of play".
Berbizier will trim the squad down to 30 before the tournament, which the Azzurri will be seeking to reach the quarter-finals of for the first time.
Italy are in Pool C, along with Scotland, New Zealand, Romania and Portugal.
They are expected to vie with Scotland for the group's second qualifying slot behind the mighty All Blacks.
The crunch game between the nations takes place in St Etienne on September 29.
Here is the squad: Matias Aguero (Arix Viadana, 6 caps)
Robert Barbieri (Overmach Cariparma, 5 caps)
Mauro Bergamasco (Stade Francais, 57 caps)
Mirco Bergamasco (Stade Francais, 42 caps)
Valerio Bernabo' (Cammi Calvisano, 9 caps)
Marco Bortolami (Gloucester, 59 caps) - captain
David Bortolussi (Montpellier, 8 caps)
Kristopher Burton (Orleans, 2 caps)
Gonzalo Canale (Clermont-Auvergne, 31 caps)
Pablo Canavosio (Castres, 14 caps)
Martin Castrogiovanni (Leicester Tigers, 43 caps)
Roland De Marigny (Cammi Calvisano, 15 caps)
Carlo Antonio Del Fava (Bourgoin, 21 caps)
Santiago Dellape' (Biarritz Olympique, 43 caps)
Paul Derbyshire (Rolly Gran Parma)
Carlo Festuccia (Rolly Gran Parma, 38 caps)
Alessio Galante (Rolly Gran Parma, 2 caps)
Ezio Galon (Overmach Cariparma, 10 caps)
Leonardo Ghiraldini (Cammi Calvisano, 4 caps)
Paul Griffen (Cammi Calvisano, 34 caps)
Andrea Lo Cicero (Infinito L'Aquila, 66 caps)
Andrea Masi (Biarritz Olympique, 30 caps)
Carlos Nieto (Gloucester, 21 caps)
Ludovico Nitoglia (Cammi Calvisano, 17 caps)
Fabio Ongaro (Saracens, 48 caps)
Silvio Orlando (Benetton Treviso, 13 caps)
Luciano Orquera (Brive, 10 caps)
Sergio Parisse (Stade Francais, 42 caps)
Enrico Patrizio (Carrera Petrarca Padova, 1 cap)
Salvatore Perugini (Stade Toulousain, 42 caps)
Ramiro Pez (Bayonne, 37 caps)
Matteo Pratichetti (Cammi Calvisano, 6 caps)
Kaine Robertson (Arix Viadana, 21 caps)
Alberto Sgarbi (Benetton Treviso)
Josh Sole (Arix Viadana, 19 caps)
Marko Stanojevic (Bristol, 5 caps)
Fabio Staibano (Overmach Cariparma, 6 caps)
Alessandro Troncon (Clermont-Auvergne, 95 caps)
Maurizio Zaffiri (Cammi Calvisano, 14 caps)
Alessandro Zanni (Cammi Calvisano, 15 caps)
Manoa Vosavai (Overmach Cariparma)
