Rome - Roger Federer's French Open problems piled up on Thursday when he was dumped out of the Rome Masters by Frenchman Richard Gasquet.
World No 3 Federer went down 4-6, 7-6 (7/2), 7-6 (7/4) in the third round, a worrying setback just 10 days before the start of Roland Garros, the second Grand Slam of the season.
Nadal, the defending French Open champion, quickly put behind him what he described as his worst clay performance in memory on Wednesday to streak into the quarter-finals with a 6-4, 6-2 win over compatriot Feliciano Lopez.
Federer broke Gasquet in the seventh game of the first set before serving it out and when he broke again in the fifth game of the second, it looked like he would be in for a short afternoon.
But Gasquet displayed previously unseen grit and determination to fight back in the eighth game and then take the tie-break.
The decider also went to a tie-break that saw two early mini-breaks apiece before Gasquet took the initiative when Federer missed a backhand.
Leading 5-4 and with two serves to come, Gasquet held his nerve while Federer made errors off both wings to hand the match to the Frenchman.
It was only Gasquet's second victory against the record 16-time Grand Slam winner in 10 meetings, his first coming in 2005 in Monte Carlo in their first match when he was still a teenager.
In the Ladies section, French Open champion Francesca Schiavone showed her mettle as she came back from a set down to beat Daniela Hantuchova 3-6, 6-2, 7-5 in a two and a half hour marathon to reach the quarter-finals for the fourth time, but the first since 2005.
Former Wimbledon champion Maria Sharapova breezed past 10th seed Shahar Peer 6-2, 6-2.
There were mixed fortunes for the two Australian women remaining in the draw as sixth seed Samantha Stosur put an end to Slovenian qualifier Polona Hercog's impressive run, winning 6-3, 6-4.
However, Jarmila Gajdosova was soundly thrashed by Chinese fourth seed Li Na, 6-1, 6-2.
Twice champion and former world number one Jelena Jankovic was made to fight before overcoming Spanish qualifier Anabel Medina Garrigues 6-4, 2-6, 6-2.
Results from the fifth day of the ATP/WTA Italian Masters (x denotes seeding):
Rafael Nadal (ESP x1) bt Feliciano Lopez (ESP) 6-4, 6-2
Marin Cilic (CRO) bt Mardy Fish (USA x11) 7-6 (8/6), 6-3
Richard Gasquet (FRA x16) bt Roger Federer (SUI x3) 4-6, 7-6 (7/2), 7-6 (7/4)
Tomas Berdych (CZE x7) bt Jarkko Nieminen (FIN) 6-2, 6-7 (4/7), 6-2
Florian Mayer (GER) bt Juan Ignacio Chela (ARG) 7-5, 6-4
Andy Murray (GBR x4) bt Potito Starace (ITA) 6-2, 6-3
Jelena Jankovic (SRB x5) bt Anabel Medina Garrigues (ESP) 6-4, 2-6, 6-2
Maria Sharapova (RUS x7) bt Shahar Peer (ISR x10) 6-2, 6-2
Greta Arn (HUN) bt Elena Vesnina (RUS) 3-6, 7-6 (7/3), 7-6 (7/3)
Li Na (CHN x4) bt Jarmila Gajdosova (AUS) 6-2, 6-1
Samantha Stosur (AUS x6) bt Polona Hercog (SLO) 6-3, 6-4
Francesca Schiavone (ITA x2) bt Daniela Hantuchova (SVK) 3-6, 6-2, 7-5