Co-creator Damon Lindelof reveals the "Mulholland Drive" star was one of the people he had in mind to portray spinal surgeon Jack Shephard on the survival series, but he politely turned down the opportunity - and the role eventually went to Matthew Fox.
"Justin looking and sounding the way that he does, instantly the town [Hollywood bosses] decides, 'We're going to groom this guy to be the star of a Marvel movie,' " producer and screenwriter Lindelof told Esquire magazine as part of a Theroux cover story.
"There's a reason that you look at his filmography and there aren't twenty-five movies and TV shows that he's worked on. It isn't for a lack of opportunity. It's because he's very selective about what he chooses to do."
He added, "When we were casting 'Lost', he was definitely on the Jack list. He wasn't interested."
Instead, Theroux decided to hone his writing skills and went on to release Hollywood satire "Tropic Thunder" - a move which came as a shock to Lindelof.
"It was like, 'Oh my God, Justin Theroux's a comedy writer?' " he recalled.
The two would eventually find the right opportunity to work together on another TV drama, "The Leftovers", in 2014, although Lindelof wasn't sure Theroux was quite right for the main part of Kevin Garvey.
"I was like, 'That guy is way too good-looking to pull it off,' " he remembered. "Then he came in and read, and I was like, 'This guy is a very, very, very good actor, in spite of his good looks.' "