A group of masked men have made away with a large number of handguns after holding up a weapons shop in Melbourne's north yesterday morning.

Four men, armed with firearms and sledgehammers, stole a large number of guns from O'Reilly's Firearms on High Street in Thornbury shortly before 11am yesterday, according to police.

It has been reported the number of guns stolen could be more than 65.

The thieves fled the gun shop in a stolen car, which was later found burnt out in nearby street.

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Assistant Commissioner Steve Fontana told reporters in Melbourne the armed robbery appeared to have been carefully planned.

"The offenders have done their planning before they've gone in," he said.

"They knew what they were looking for, so this wasn't just an opportunistic type of offence."

The male staff member who was behind the counter at the store at the time of the robbery was not physically injured.

Fontana said police at this stage did know who the offenders were, but appealed to members of the public to help with their investigation.

"We are seeking support from any witnesses that may have seen the offenders in the lead-up to this offence in High St, Thornbury, or in Clapham St, Thornbury, where the stolen vehicle was eventually dumped this morning," he said.

Investigations in the incident are being led by the armed crimes squad.

"This has been given a very high priority, we are concerned because there were a large number of handguns stolen," Fontana said. "We're putting all our resources into recovering these firearms and charging the offenders responsible."

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The assistant commissioner said the armed robbery was "highly unusual", but said investigators "normally find" there is "some sort of organisation" behind such a targeted robbery.

He said the stolen weapons would be "worth a lot of money on the black market".

"These are easily concealable. They're lethal weapons, basically," Fontana said. "A number of criminals have taken it to deliberately enter that store with weapons and steal them. They're obviously going to be recycled back for criminal intent."