The 29-year old Glaswegian snatched an eagle and five birdies in a four-under-par 68 to move to 15 under in the elite 33-player field on the rain-soaked Durban Country Club course.
Jamieson was in South Africa's third-largest city only a month ago and breaking through to capture his first Tour title, the Nelson Mandela Championship. Now the quietly-spoken Scot, ranked 100th in the world, is in position to take the Durban Double.
If he does, he will soar into the world top 50 and earn himself a Masters invitation if he can hold that place to mid-March, to join fellow Scots Sandy Lyle and Paul Lawrie.
"I used to attend college at Augusta State and I've managed to play Augusta National five times, which was special," he said. "So to go back there and compete in the Masters would be special but that is a long way down the road and all I am doing is staying in the present.
"But then if someone had mentioned to me I would be taking a five-shot lead into the last round of this event I would be quite surprised, for sure - there are so many great players here."
Scott shrugged off suggestions he now has something to prove given heavy rain had reduced the Nelson Mandela Championship to 54 holes.
"I don't care if anyone's got a problem saying that winning over two rounds wasn't a real win so that doesn't bother me," he said. "Let those saying that come out here and try to win on the European Tour and the position I am in now can't get any better than this given the number of great champions in the field.
"If I did win I guess it might be some validation if anyone does doubt me, but I don't think I have anything to prove. And besides, I was one of the highest-ranked players in the Nelson Mandela event. Maybe now if I do win tomorrow they might hand me the keys to the city."
A win would also qualify him for next month's $8.75 million WGC-Accenture Match-Play Champ-ionship and a start in August's similar cash-prize event, the WGC-Bridgestone Invitational.
For three days Jamieson has seen off three big names. He played the first round in the company of double Open champion Pádraig Harrington and finished a shot ahead of the Irishman.
On day two he was six shots lower than Dane Thomas Bjorn and on day three he pulled the rug out from under crowd favourite Louis Oosthuizen, with the Open champion signing for a 74 to drop back to a share of second.
Jamieson added: "Most of the guys played well today, but Thomas and Pádraig, I think they played fairly well when I played with them. You always have your eye out, comparing yourself to them, but yeah, I managed to beat them both through the week so that was nice."
Frenchman Julien Quesne (67), Thailand's Thongchai Jaidee (67) and Oosthuizen share second place on 10 under par. Lawrie posted a second straight 70 to move to seven under par while Colin Montgomerie also had a 70 but is well down the board at four over.