A staggering 40 million euros ($A58m) worth of diamonds and other jewels have been stolen from the luxurious Carlton Hotel in Cannes on the French Rivieria.
The crime is one of Europe's biggest jewellery heists in recent years, police say.
One expert noted the crime follows recent jail escapes by members of the notorious "Pink Panther" jewel thief gang.
The hotel in the sweltering French Riviera was hosting a jewellery exhibit from the prestigious Leviev diamond house, which is owned by Israeli billionaire Lev Leviev.
A police spokesman says the theft took place around noon on Sunday, but he could not confirm local media reports that the robber was a single gunman who stuffed a suitcase with the gems before making a swift exit.
The Carlton Hotel featured prominently in Alfred Hitchcock's Academy Award winning film, To Catch a Thief, which starred Cary Grant as a reformed cat burglar chasing a jewel thief on the French Rivieria.
It is situated on the exclusive Promenade de la Croisette and is patronised by the rich and famous throughout the year. The hotel's position provides not only a beautiful view of the sea but also an easy getaway for potential jewel thieves on the long stretch of road.
Jonathan Sazonoff, US editor for the Museum Security Network website says the likelihood of recovering the stolen diamonds and jewels is slim, because the thieves can easily sell them. "They can be broken up and so they can be easily smuggled and sold."
Cannes appears to be a favourite target this year - in May it was struck by other two jewellery heists during the Cannes Film Festival.
Police will likely probe whether Sunday's heist is linked to recent jail escapes by alleged members of the Pink Panther jewel thief gang.
On Thursday, gang member Milan Poparic escaped his Swiss prison after accomplices rammed a gate and overpowered guards with their AK-47s.
Police say the "Pink Panther" network's members are prime suspects in a series of daring thefts. According to Interpol, the group has targeted luxury watch and jewellery stores in Europe, the Middle East, Asia and the United States, netting more than 330 million euros since 1999.
Poparic is the third member of the Pink Panthers to escape from a Swiss prison in as many months.
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