ABC News' Z. Byron Wolf and Sarah Parnass report:
Call it the second curse of the Bambino.
Tuesday's defeat made Mitt Romney the third straight presidential nominee from Massachusetts to lose on Election Day.
For almost nine decades, Bay State residents suffered under the Curse of the Bambino - the belief that the sale of Babe Ruth by baseball's Boston Red Sox prevented the team from winning a championship for almost a century.
Little did they know that a new curse started about halfway through that time.
Since the death of President Kennedy in 1963, no Massachusetts politico has made a successful bid for the White House.
Three clinched their party's nomination: former Massachusetts Gov. Michael Dukakis in 1988, Sen. John Kerry of Massachusetts in 2004; and now Mitt Romney.
But all three failed to win it in the playoffs.
Those who serve the Massachusetts commonwealth can be senators, congressmen, governors and diplomats - but not presidents.
Sometimes, the commander-in-chief grew up there. It's been possible to win the presidency if you attended high school in Massachusetts, as did the two President Bushes, but you must first leave there and make your name elsewhere.
Presidents go to Massachusetts for college. President Obama and George W. Bush both studied at Harvard University in Cambridge, Mass.
But even Teddy Kennedy - a Massachusetts politician from one of America's most beloved families - couldn't make it past a Georgia peanut farmer from his own party. Read about the interview that preceded his campaign's disintegration there.
What might the curse mean in 2016?
It's a bad omen for Elizabeth Warren, the Massachusetts Democrat who just won a Senate seat from popular Sen. Scott Brown, R-Mass.
It doesn't look good for Massachusetts Gov. Deval Patrick, either, though his impassioned speech at the Democratic convention put him in the spotlight as a potential presidential pick. ( Read about Patrick's plans for 2016 here)
And it might prevent Kerry from considering a second shot at the Oval Office.
But how long can the curse last? The first Curse of the Bambino was said to have originated when the Red Sox sold Ruth to the Yankees in 1919.
Bostonians declared the curse over in 2004, when their team won the World Series for the first time in 86 years.
Following that timeline, we shouldn't expect to see a Massachusetts man or woman take the presidency before 2048.