Police said a 23-year-old man was working in the Neville Store in the Calderwood area East Kilbride when the thief entered the shop.
He threatened the shopkeeper with a knife and demanded cash, before making off with a three figure sum of money. He ran off towards Stratford. The shopkeeper, although uninjured, was shaken by the ordeal.
The incident happened around 9.15am yesterday. Police believe the robber was seen hanging around near Long Calderwood Primary before the incident.
The man is described as around 5ft 10in, of medium build, wearing jeans and a dark or black jacket with the hood up. He had a laptop style bag over his shoulder and a mask covering his face.
Detective Inspector David Scott, of East Kilbride CID, who is leading the inquiry, said: "We're continuing extensive inquiries into this incident, including accessing all available CCTV in the local area. We've also been carrying out door to door inquiries.
"The man responsible was seen hanging around the local area, particularly around Long Calderwood Primary School, just prior to the robbery taking place.
"Were you dropping your children off to school around 9am and did you see a man fitting the description? You may be able help with our inquiries."
Anyone with information is asked to call East Kilbride CID on 01355 564 000.