Top-ranked Aryna Sabalenka suffered a shock third-round loss to Sorana Cirstea at the Italian Open, as defending champion Jasmine Paolini also made an early exit.
Sabalenka appeared to be cruising to victory while leading by a set and 2-0 but the 26th-ranked Cirstea stormed back to triumph 2-6 6-3 7-5.
It was a first win over a world No 1 for the 36-year-old Romanian, who is playing her final pro season.
"I'm very, very happy," Cirstea said. "Aryna is an amazing player. I thought I played really well today. I'm working really, really hard. It's nice to have this result as payoff."
Sabalenka appeared visibly bothered by lower back pain and called for a medical time out for treatment while down 4-3 in the final set.
"Felt like my body was limiting me from performing on the highest level," Sabalenka said. "She stepped in and played incredible tennis. Didn't really give me much opportunities…I guess we never lose, we only learn, so it's okay.
"Probably it's my lower back, connected to the hip, which is limiting me from the full rotation. We are going to have some days off, spend it on recovery. That's the plan for now."
It was the second straight surprise exit for Sabalenka, who was upset by American Hailey Baptiste in the Madrid Open quarter-finals last week, with Cirstea progressing to play Linda Noskova in the last 16.
Defending champion Jasmine Paolini was eliminated after the Italian wasted three match points in a 4-6 7-6 (5) 6-3 loss to Elise Mertens, while third seed Coco Gauff survived a significant scare before eventually beating Argentinean Solana Sierra 5-7 6-0 6-4.
Jannik Sinner made a successful start to his bid to win all nine Masters 1000 events and complete the 'Career Golden Masters' by beating Austria's Sebastian Ofner 6-3 6-4 in the second round.
The top seed and world No 1 made history last week in Madrid by becoming the first player to lift the winner's trophy at five straight ATP Masters 1000 events, having also triumphed in Paris, Indian Wells, Miami and Monte-Carlo in recent months.
A Career Golden Masters would put him alongside Novak Djokovic as the only players to achieve the feat since the series began in 1990, with Sinner's winning start his 29th successive win at a Masters event.
Sinner never faced a break point in the 91-minute victory and last year's runner-up will next face either Czech world No 26 Jakub Mensik - the last player to beat the Italian - or Australia's Alexei Popyrin.
"It is an amazing feel to be back," Sinner said. "The first match, the most important thing is not to lose. The level will eventually come day by day. I am very happy to be here. Since day one, this has been a very special tournament for me."
Elsewhere, British involvement in this year's event ended when Cameron Norrie was eliminated after a 6-3 7-5 loss to Argentina's Thiago Agustin Tirante in the second round.
Ben Shelton's struggles on clay continued as the fifth seed lost 6-4 6-7 6-3 to Georgian qualifier Nikoloz Basilashvili, while world No 5 Felix Auger-Aliassime struggled with a leg issue during his straight-sets defeat to Mariano Navone.
Seventh seed Daniil Medvedev advanced via walkover after Tomas Machac pulled out due to illness.
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