World number two Kim Clijsters suffered a surprise 6-4, 7-6 defeat by Russian Dinara Safina in the last 16 of the Italian Open on Thursday.
The Belgian's exit -- following the withdrawals of world number one and defending champion Amelie Mauresmo, Nadia Petrova and Maria Sharapova due to illness and injury -- left the claycourt tournament without the world's top four players.
Safina, seeded 16, had failed to win a set in her six previous matches with Clijsters but ended that run as the Belgian struggled to find the range on her groundstrokes.
The Russian grabbed an early break in the second before Clijsters steadied herself in the fourth game, hitting a succession of winners to break back.
The errors crept back into Clijsters's game in the tiebreak, a slew of backhand errors gifting victory to Safina.
"I came out on court a little bit tired after playing doubles last night, but when I saw that she was not playing well I said to myself I have to go for it," said Safina, who next plays fifth-seeded Russian Elena Dementieva.
"She is a great baseliner and she hits the ball so hard, so you have to wait and take whatever chances come your way."
Safina was joined in the quarter-finals by former world number one Martina Hingis, who beat eighth seed Francesca Schiavone 6-0 7-5.
The 25-year-old Swiss, who recently returned to the top 30 after ending a three-year exile, easily overpowered the top-ranked Italian in a one-sided first set.
Schiavone came out more aggressively in the second set to grab an early break before Hingis broke back.
She then took advantage of a double fault and a pair of wild backhands by Schiavone to gain a decisive break in the 11th game before serving out for the match.
"In the first set I played very well, I made almost no mistakes. But then in the second set she started to mix it up and all I was thinking was how I didn't want to go to a third set," said Hingis, who won the claycourt tournament in 1998.
In the last eight Hingis will play the winner of the later match between 15th seed Flavia Pennetta and Anabel Medina Garrigues.