World No 3 Roger Federer pulled out of the Italian Open before his quarter-final match on Friday with a right leg injury.
Federer, a four-time Rome finalist, had been due to meet Greek eighth seed Stefanos Tsitsipas for a place in the semi-finals.
The Swiss 20-time grand slam winner was playing in Rome to prepare for his return to the French Open for the first time since 2015.
"I am disappointed that I will not be able to compete today," Federer said. "I am not 100 percent physically and after consultation with my team, it was determined that I not play.
"Rome has always been one of my favourite cities to visit and I hope to be back next year."
Federer had been on court nearly four hours on Thursday as competitors played two matches after rain delays midweek.
The 37-year-old saved two match points to win through 2-6, 6-4, 7-6 against Borna Coric to advance to the quarter-finals after earlier easing to a straight sets win over Portgual's Joaa Suosa.
The former world No 1 had been a late addition to the Rome tournament as he sought clay-court practice ahead of his bid to add to his lone French Open title in 2009.
Tsitsipas will play either defending champion Rafael Nadal or Fernando Verdasco for a place in the final.