The Roma man has been a mainstay of the Italy side throughout an accomplished career, the highlight of which remains a winners' medal from the 2006 FIFA World Cup.
A group stage exit meant the most recent global showpiece in Brazil was one to forget for De Rossi and co and they face a stern test of their recovery process against Croatia - a nation Italy have not beaten in their past six attempts.
"For me it’s incredible to reach the 100-cap mark with Italy shirt – it's a honour I'll keep in my heart until the end of my career," the 31-year-old said at a press conference
"But I'd like a youngster to overtake me [in the all-time list]."
Both teams head into De Rossi's landmark match with three wins from three so far in Group H, but Italy were far from convincing in their one-goal victories over minnows Azerbaijan and Malta.
One man not involved in those matches was Mario Balotelli, who earned a surprise recall to the national squad in light of his disappointing form since joining Liverpool from Milan in August.
Despite the forward's controversial image, De Rossi insists Balotelli is no problem behind the scenes.
"He's not the kind of guy who causes problems in the dressing room," he said.
"He might be exuberant and sometimes go about his business in a particular way, but fundamentally he’s good natured.
"With Mario there is a good rapport."
Balotelli might have to wait on the bench for his return to the international fold, with Borussia Dortmund's Ciro Immobile favourite to be paired with Graziano Pelle in attack.
Pelle marked his debut in Malta with the only goal of the game, while Leonardo Bonucci was sent off to rule him out of this encounter.
Conte's options alongside De Rossi in midfield are not as plentiful, with Andrea Pirlo and Marco Veratti (both thigh) absent alongside long-term absentee Ricardo Montolivo.
Croatia are particularly strong in the middle of the park and star men Luca Modric and Ivan Rakatic should be fresh after they were rested for Thursday's 2-1 friendly defeat against Argentina in London.
Striker Mario Mandzukic and defender Dejan Lovren are also set to bolster the line-up that took an early lead through Anas Sharbini but were beaten by Cristian Ansaldi's deflected effort and a Lionel Messi penalty.
Former Croatia and Milan midfielder Zvonimir Boban, now a pundit on Italian television, believes his nation could find Conte wanting tactically and continue their impressive run in Italy.
Boban told Sky Italia: "[Conte] struggles against opponents with good wingers, who are able to switch play quickly.
"Big teams don't have any problems doing that. You can't dominate or set a trend with 3-5-2.
"The only great game Conte's Juventus played in Europe was against Real Madrid, when they switched to a 4-3-3."
