With fellow Italian Francesco Molinari able to follow up his first round 62 with "only" a 70, Manassero's scintillating seven birdies in the last nine holes brought him only one off the lead in the Aberdeen Asset Management Scottish Open at Castle Stuart.
The Tour's youngest-ever champion could qualify for Royal Lytham next week with a top five finish, but his sights are on emulating what German Marcel Siem did at the French Open last Sunday by winning to earn his spot.
"The Open is on my mind and this is my last chance," said the 19-year-old from Verona, who stands 11 under par at halfway.
Molinari had a triple bogey seven on the 464-yard seventh to allow Swede Alex Noren to join him out in front after a second successive 66 the day after his 30th birthday and the day after his girlfriend Emelie won an event in Norway.
Argentina's big-hitting Ricardo Gonzalez is joint third with Manassero, while world number one and defending champion Luke Donald's 68 means he has only three shots to make up and Phil Mickelson's 64 brought him just five back.
With 2009 winner Martin Kaymer alongside Donald and Padraig Harrington six under, the final 36 holes has all sorts of possibilities still.
Ernie Els survived with nothing to spare at four under - only two off the lowest-ever cut on the circuit - and it will be a weekend without Tom Lewis, Paul Casey, Paul Lawrie and Colin Montgomerie.
Lewis, the amateur star of last year's Open, will not be at Lytham after his miserable recent run continued with rounds of 73 and 72 for one over par.
Montgomerie finished one under and Lawrie two under, but Casey looks no nearer finding his old form.
A week after finishing joint last in Paris he had only three of the 156-strong field behind him after back-to-back 76s.
He has made only one cut since dislocating his shoulder snowboarding in Colorado last Christmas Eve and trying to change that in The Open is now asking a lot for the former world number three.
Manassero finished a brilliant 13th at Turnberry three years ago and adds: "I would really love to be in The Open. I like links golf and it has a special atmosphere."
Molinari stated: "Following a 62 is never easy. I tried to do the same, but I knew it was going to be hard."
He and his young fellow countryman were at the same Italian restaurant on Thursday night and followed that with a trip to McDonalds for ice creams.
Now they are rivals for a first prize of over £416,660 and a title won by Molinari's brother Edoardo two years ago.
Big things were expected of Noren when he won in Wales and in his home country last season, but he has not had a top-five finish since October and is trailing way behind in the Ryder Cup race.
"I think I'm not going to be on top at the end of the day," he said at lunchtime. But he was wrong.
There was a hole-in-one at the 168-yard 11th for the second day running. England's Andrew Johnston won 168 bottles of champagne for being the first and Scot Peter Whiteford had to settle for one magnum.
"I'll have a word - maybe he can give me a couple," said Whiteford, who shot 65 to move to eight under.
Manassero is not the only 19-year-old to make it through.
Scottish amateur Jack McDonald, playing in the final group of the day, chipped in at the par-five last to earn himself another two rounds on his Tour debut.