Tambellini finished 36 holes at 13-under 130 for a three-stroke lead over Garth Mulroy (66), David Branshaw (66), Paul Claxton (66), Jason Enloe (69) and Kyle Reifers (72), who are all knotted at 10-under 133.
A two-time winner on tour, Tambellini played the par-71 Georgian Bay Club on Friday, the same course that will host the final two rounds over the weekend. Raven Golf Club, a par-72 layout, co-hosted the first two rounds.
Tambellini, whose last victory came in 2005, made his run Friday with a spectacular 10-hole stretch during which he made seven birdies. He sandwiched two bogeys around those birdies.
The 34-year-old said he turned his brain 'off' during the run.
'That's really what I've been working on, almost having a blank mind out there,' said Tambellini. 'I'm thinking about the target and that's it. I'm focusing more about swing feels than swing thoughts.'
Through 36 holes, Tambellini has missed only three fairways and four greens. He has needed only 29 putts in each of his first two rounds.
A former member of the PGA Tour for two seasons, Tambellini has only held the 36-hole lead once before ' at the 2003 Albertsons Boise Open, where he claimed his first win.
'I didn't really think about much out there today,' said Tambellini. 'That's what happens when you play well ' you just kind of hit it around and it goes in.'
The cut line fell at 3-under 140 with 67 players moving on to the weekend.
Defending champion Justin Hicks was among those who missed the cut.