Burglars broke into a high-value vault in central London and emptied up to 70 safety deposit boxes by climbing down the lift shaft, Scotland Yard said.
The raiders disabled a second floor lift and climbed down the shaft to enter the basement of Hatton Garden Safe Deposit Ltd at the weekend.
A heavy duty drill was used to bore holes into the 6ft (2m) thick vault walls reinforced with concrete.
Many of the deposit boxes are thought to belong to uninsured local jewellers.
Det Ch Insp Paul Johnson said there was a "chaotic" scene in the vault, where a number of tools had been left behind, including an angle grinder, concrete drills and crowbars.
One of the tools used was a DD350 drill worth about £3,500. Experts said it was likely the thieves made several holes until they had created a big enough space to get through, which would have taken an experienced operator several hours.
The area is known for its gold and diamond trade and many local jewellers used safety deposit boxes to store their stock in after they had finished trading for the day.
A lot of the company's clients may not have insured their deposit boxes against theft, Graeme Trudgill, executive director of the British Insurance Brokers' Association said.
He predicted local jewellers could be left millions of pounds out of pocket.
"One man tells me he's lost several hundred thousands pounds in the heist," BBC Home Affairs correspondent Danny Shaw tweeted.
The victim had apparently stored jewels and watches there for five weeks following his retirement.
The owners of the other boxes are being contacted to find out what else may have been stolen.
Michael Miller from Knightsbridge, London, said he "felt sick" that he may have lost up to £50,000 worth of uninsured jewellery, including an irreplaceable timepiece he bought when his son was born.
Police said there was no sign of forced entry to the building, which is shared by a number of other companies. Scotland Yard said it had not ruled out insider knowledge.
"We've just got the vault open and there's security boxes on the floor and it's covered with dust and debris," Det Ch Insp Paul Johnson told a news conference earlier.
He described it as an "organised" operation and said getting to the bottom of what happened would be a "painstaking and meticulous" process.
No arrests have been made.