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 temporary jewelry exhibit over the summer from the prestigious Leviev diamond house, which is owned by Israeli billionaire Lev Leviev.
A police spokesman said the theft took place around noon, 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 spokesman spoke on condition of anonymity because he was not authorized to discuss the matter on the record.
It is situated on the exclusive Promenade de la Croisette that stretches a mile and a half (2.4 kilometers) along the French Riviera, and is thronged 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 along the long stretch of road.
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"It's a huge theft. Anytime you talk about a heist with many millions of dollars it turns heads and feeds the imagination," said Jonathan Sazonoff, US editor for the Museum Security Network website and an authority on high-value crime.
"The fear is, if you're dealing with high-quality minerals, it's hard to get them back," Sazonoff said. "They can be broken up and so they can be easily smuggled and sold."
The valuable gems were supposed to be on public display until the end of August. It was not immediately clear how many pieces were stolen.
Several police officers were placed in front of the Carlton exhibition room near a Cartier diamond boutique to prevent the dozens of journalists and photographers from getting a look at the scene of the crime.
Europe has been struck by several brazen jewelry thefts in recent years, some of which have involved tens of millions of dollars in treasure.