A "large" number of "lethal" handguns have been stolen in a well-organised "targeted attack" on a Melbourne gun store, Victoria Police says.

Four armed men wearing masks, one with a gun, and at least one other carrying a sledgehammer, entered the High St shop at Thornbury, in Melbourne's north, around 11:00am, stealing a number of guns from the racks.

Asked to comment on reports that up to 60 weapons may have been taken, Assistant Commissioner Steven Fontana said they did know it was more than a dozen but the final total would not be known until a thorough audit had been conducted.

"We do know a large number of handguns were stolen for that's for sure," he told a press conference.

The armed men fled in a white stolen SUV which was later found dumped on Clapham St, Thornbury.

O'Reilly's Firearms was targeted in the armed robbery, police said. ( ABC News: Stephanie Anderson )

Police have no suspects or descriptions of the wanted men and are appealing to anyone who may have seen them before or after the incident, to contact Crime Stoppers.

Assistant Commissioner Fontana said the investigation was a "high priority" given the number of weapons stolen.

"This was a targeted attack. The offenders have done their planning before they've gone in," he said.

"They knew what they were looking for. This wasn't just an opportunist-type offence. It was clearly targeting that particular shop to get these weapons.

"They're obviously going to be recycled back for criminal intent."

Assistant Commissioner Fontana said solving the case was a "high priority" for police. ( ABC News: Stephanie Anderson )

He called it a "highly unusual" offence and said it was hard to say how much the guns were worth because they are "quite expensive" and in demand by criminal groups.

"It's a large number of handguns. These are easily concealable and they're lethal weapons basically and some, a number of criminals have taken it to deliberately enter that store with weapons and steal them," he said.

"They're in the hands of criminals and that's the biggest concern."

The investigation is "a high priority for us" Assistant Commissioner Fontana said, with support from the state anti-gangs and illicit firearms teams.

"We'll be using all our resources to track these guns down and the offenders responsible," he said.