People: Not too much green where Ruffalo roams

Playing the romantic lead opposite Reese Witherspoon, Jennifer Aniston and Meg Ryan should generate big box office at least once, right?

But for Mark Ruffalo, “big” and “box office” have never met.

Ruffalo has overcome so much, including a brain tumor and years of fruitless auditions, that he could be the Ironman of thespian endurance. At 39, he is considered one of Hollywood’s most talented denizens without a hit.

“My wife says I have bad taste,” Ruffalo says. “I just don’t know what it would look to have a movie that would make $150 million, you know?”

His new film, “Zodiac,” a retelling of the real-life Zodiac killer’s rampage in California, reserves the juicy parts for guys, including Ruffalo’s Detective David Toschi.

Toschi was not a public figure, so Ruffalo didn’t have to be spot-on in re-creating the character. But that wouldn’t be Ruffalo.

“It mattered incredibly to me,” he says. “You’re talking about a man whose life was deeply tied into this specific case. He suffered greatly from the outcomes of it.”

Since his breakout performance in “You Can Count On Me” (2000), Ruffalo has earned critical acclaim while his movies have been met with shrugs from ticket-buyers.

Even the hyped outings with A-list actresses – “Just Like Heaven” with Witherspoon, “Rumor Has It” with Aniston, “In the Cut” with Ryan, not to mention “13 Going on 30” with Jennifer Garner – failed to drum up significant numbers.

“Collateral” and “Eternal Sunshine of the Spotless Mind” were successful, but with Ruffalo in supporting roles.

Like everyone else with an unstable income, Ruffalo is downsizing. Work on the home that he shares with his wife, Sunrise Coigney, and their young children, Keen and Bella, has ceased.

“The past year or so has been a simplification of our lives,” he says. “I think it’s important for kids to have a simpler life, especially living in Hollywood. Their comfort is on my mind, but we’ve made a conscious decision that I wouldn’t do anything I didn’t want to do just because we needed the money.”

Last spring, Ruffalo essentially removed himself from the movie loop while submitting a Tony-nominated turn as an amputee in Clifford Odet’s “Awake and Sing!”

It was his Broadway debut. “That buried me,” he says.

He has surmounted a far greater obstacle offstage. A cyst lodged in his brain paralyzed part of Ruffalo’s face in 2002.

Now fully recovered after surgery, he says, “It’s integrated into who I am now. It isn’t something I think about all the time.

“It’s pretty much in the rear-view mirror, but it’s sort of one of those defining moments in life, like having my kids, getting married, ‘You Can Count on Me.’ It’s just another one.”

The birthday bunch

Singer Miriam Makeba is 75. Actress Catherine O’Hara is 53. Actress Patricia Heaton is 49. Actor Mykelti Williamson is 47. Actor Steven Weber is 46. Singer Evan Dando (The Lemonheads) is 40. .Actress Andrea Bowen (“Desperate Housewives”) is 17.