Molinari leads Dubai Desert Classic as McIlroy struggles
Former British Open champion Molinari, now 418th in the world rankings, made eight birdies in a seven-under par 65.
The 43-year-old Italian is two shots clear of Sweden's Mikael Lindberg, with Swiss player Joel Girrbach and South African JC Ritchie a stroke further back.
It was Molinari's lowest round on the European Tour since January 2024.
"It's been a long time. I've changed everything and then I've changed back," said the 2018 Ryder Cup winner, who has not won a professional title since the Arnold Palmer Invitational seven years ago.