Answer: When Mitt Romney shifts his focus to the candidate -- in this case, Rick Santorum -- to the near exclusion of the rest of the field.
The former U.S. senator from Pennsylvania was three-for-three on Tuesday -- claiming wins in Colorado, Minnesota and Missouri -- and poking holes in Romney's invincibility armor to boot. Almost immediately anti-Santorum attack ads from the Romney camp appeared.
"That's always a good sign," Santorum told CBS News during a campaign swing in Texas.
While in Oklahoma, Santorum lit into Romney, who he accused of "serially tearing down opponents without offering any kind of vision for what he wants to do for this country."
Santorum says his three wins last week -- he was awarded the win in Iowa, too -- shows that people "are likin' the message and the messenger."
He won Tuesday by rallying conservatives to his cause in three states that are considered battle grounds in November. Even former Minnesota Gov. Tim Pawlenty, a GOP-presidential-hopeful-turned-Romney-supporter, couldn't deliver his state to Romney, who finished a distant third behind Santorum and U.S. Rep. Ron Paul of Texas.
And as Romney once took on President Obama on the stump, so, too, is he taking on Santorum.
"I stand here to be the conservative alternative to Barack Obama," he said during a post-Tuesday rally.
Polls show Santorum surging and leading in several states, including his home state of Pennsylvania, with an April 24 primary, and Tennessee, a participant in Super Tuesday March 6.
Two national polls -- Public Policy Polling and Gallup -- show Santorum either taking over the lead among Republican voters nationally or at least tied with Romney. A new Fox News poll also showed Santorum was in a dead heat with Romney.
A RealClearPolitics.com average of four polls Friday showed Romney still leading, with 33.6 percent, former House Speaker Newt Gingrich second with 22 percent, Santorum in third with 19.8 percent and Paul in fourth with 14.2 percent.
In a state that should be considered in the Romney win column -- Michigan, where his father was governor -- Santorum is giving him a run for his money. Observers told The Washington Post Santorum's hardscrabble western Pennsylvania roots may resonate with Michigan's embattled autoworkers -- just as Romney's newspaper commentary stating his opposition to the federal bailout of the auto industry may turn them off.
"I don't think this was as much an endorsement of Rick Santorum as it was another wake-up call for Governor Romney that he needs to be more specific about why he wants to be president, beyond that he's a successful businessman," Richard Wadhams, a former chairman of the Colorado Republican Party, who caucused for Romney, told The Boston Globe.
Still, Republicans have expressed concern about Romney's ability to tap into conservatives' anger and turn it into support for his cause.
David A. Keene, who is president of the National Rifle Association and was chairman of the American Conservative Union said Romney hasn't really lit a fire under the Republican base, but is making progress.
While unfair, Keene said, "the book on Romney is that he's just a technocrat and he doesn't really connect."
Also, Romney's past support for abortion rights, gun control and gay rights never sat well with grass-roots conservatives.
The New York Daily News said Tuesday's elections provide at least three big takeaways for Santorum:
He can boast that he is the conservative alternative to Gingrich, with whom he was jockeying for votes on the right. (Gingrich did poorly in Minnesota and Colorado and wasn't on the ballot in Missouri.)
With four wins, Santorum can argue that conservatives aren't rallying around Romney as their choice.
Most important, he can tell pundits, observers, other candidates and anyone else, don't count me out.
"There's an anybody-but-Mitt crowd," Chuck Laudner, a conservative Iowa Republican operative who is working on Santorum's behalf, told The Washington Examiner. "There's an anybody-but-Newt crowd. There's an anybody-but-Obama crowd. But there's no such thing as an anybody-but-Rick crowd."
That made appearances before the Conservative Political Action Conference in Washington all the more critical for Santorum and Romney.
Romney needed to convince attendees he's got the conservative chops he claims he has. Santorum had to win over those who doubt whether he can beat Obama in November.
"Romney's real mission is to win the soul of his party," Alex Castellanos, a GOP strategist who advised Romney's 2008 presidential campaign, told The Hill. "Santorum doesn't even need to run negatives against Romney, which is telling."