There are really only two obstacles to Newsom's jumping into the Lt. Gov.'s race. One is the possibility that he might lose, but he would be the instant front runner. The other is the supposed fear of leaving the city in the hands of whatever mayor the Board of Supervisors chose. 
And according to the Chron's politics blog, he's gotten over the second hurdle:
"It's no surprise I'm looking at running for another office," he continued. "I'm out of here. I'm termed out anyway...I do take my job seriously, but I'm capable of doing a lot of things at one time. By definition, it's a skill set I must have."
He added that if people are so concerned about one of the supervisors becoming mayor for the year before the next scheduled mayoral election, maybe they shouldn't have elected them to the board in the first place.
"If it's just concern with me leaving, maybe they should look at who they elected," he said.