Nine-time champion Rafael Nadal and World No. 1 Novak Djokovic have been drawn in the same group for the French Open on Friday.
The duo could face each other at the quarter-final stage.
The Spaniard would then face a potential semi-final against third seed Andy Murray and a final against 17-times Grand Slam champion Roger Federer.
According to the ATP, Nadal will start his title defence against Frenchman Quentin Halys, while Djokovic will face Finnish Jarkko Nieminen on Sunday.
"I need to win four matches before (possibly playing Djokovic)," Nadal, who has failed to win a claycourt title in Europe this season, said after the draw at Roland Garros.
"My draw is a tough one but I hope I will be ready to fight again," added Nadal, who has suffered only one defeat on the Parisian clay, in 2009.
World number one Djokovic will probably be less than happy about the prospect of facing Nadal in the quarter-finals as he bids to win the only major title to elude.
He lost to Nadal in two of the last three finals and in an epic semi-final in 2013.
Second seed Roger Federer, chasing his first Grand Slam title since 2012, takes on a qualifier in the first round and could face Frenchman Gael Monfils in the last eight.
Murray, who beat Nadal in the Madrid Masters final this month after winning his first claycourt title in Munich the week before, begins against a qualifier and has a possible quarter-final clash against seventh seed David Ferrer of Spain.
In the women's draw, holder Maria Sharapova of Russia, the second seed, will face Estonian Kaia Kanepi in the first round and possibly former runner-up Samantha Stosur of Australia in the third.
"I just focus on the first round really," said Sharapova, who won the Rome claycourt tournament last Sunday.
"It was a great week to have under my belt. It's nice to come into a grand slam with that level of confidence.
World number one Serena Williams, who takes on a qualifier in the first round, has a possible third-round encounter against Belarussian Victoria Azarenka, a former world number one.
In the fourth round she could face sister Venus, the 15th seed, and there is a possible semi-final clash against Czech Petra Kvitova, who ended her 27-match unbeaten run this season at the Madrid Open.