The theft took place at the RS McColl shop on Pennywell Road, Muirhouse, just before 7am on Saturday.
Two men ordered the 47-year-old female shop assistant to open the safe, before making off with around 600 and a quantity of cigarettes.
It comes just days after a similar armed robbery took place at the News Express shop in nearby Trinity. Police today said they could not confirm if they are linking the two incidents.
In last week's raid an armed robber – whose face was concealed by a scarf and hood – burst in to the News Express shop in Trinity and threatened to stab a shop assistant with a foot-long knife, before making off with money and cigarettes.
The Pennywell Road store has been targeted by thieves on a number of occasions in the past and police are appealing for witnesses to come forward.
The first suspect was wearing a dark hooded top with lettering on the shoulders and white trainers, and was riding a yellow bicycle.
The second was wearing a grey beanie hat, grey tracksuit top and dark bottoms, and was riding a dark-coloured bicycle. The suspects were both described as white.
A police spokesman said: "We are eager to speak to anyone who can help us locate the suspects.
"Anyone who can assist with our inquiries is asked to contact police immediately."
Most premises in the row of shops on Pennywell Road did not open until 9am, with workers unaware of the robbery until arriving for work.
One member of staff at a neighbouring shop said: "I saw three police cars in the scheme on my way to work just before 7am. It's like a ghost town at that time in the morning.
"The shop has been robbed several times before. You just get used to it, it's the only shop that seems to get targeted here."
The manager of the shop – which reopened after the incident on Saturday – confirmed that it had CCTV.
In December 2001, a young man entered the same RS McColl shop and, while the shop assistant was distracted, grabbed a four-figure sum of money from the till.
Six years earlier in June 1995, a knifeman subjected two women to a terrifying ordeal as they arrived for work at the shop early in the morning.
The man knocked on the back door of the shop at the rear of Pennywell Court, claiming to be a delivery man. When the women opened the door he brandished a knife and forced his way inside, escaping with a four-figure sum.
The shop was also targeted by armed raiders in February 1995 when two men, wearing balaclavas, threatened two female workers with a handgun and made off with between 2000 and 4000.
The manager of the RS McColl shop urged anyone with information to come forward.