For centuries, cardinals have gathered here to elect a new Pope, and from where throngs would see the white smoke.
The Sistine Chapel in the Vatican's Papal Palace is one of the most sacred spaces of the Catholic Church.
Americans are frequent tourists, but never has a musical group from the states been invited to perform... until now.
The New Jersey based continuo arts foundation choir will be the first American choir ensemble to ever perform in the Sistine Chapel.
Candace Wicke will also be the first woman to conduct there.
"For us as a representative of the United States to have this opportunity to go over and do this is like our musical Olympics. It's standing on the podium and having the gold medal," Wicke says.
Although the choir is based in NJ, members hail from nine different states.
So, invitations to the historic concert have been sent to each state's governor, as well as to a host of dignitaries, including President Obama.
This multi-generational choir goes as young as eleven-years-old to a member in her 70s. They will perform a piece by American Film Composer Stephen Edwards called "Requiem For My Mother".
For Dana Dowd it's personal.
Years ago, she visited the Sistine with her mother who died last august.
"I know she'll be there with me in the Sistine chapel," says Dowd.
Melanie Herbert, the choirs' youngest member, it's the experience of a lifetime to possibly sing for Pope Francis who's been invited.
"I feel just so honored to sing in such a great and magnificent place. It's just so incredible," Herbert says.
Historically, the Sistine Chapel has been reserved for sacred papal events, which means these American voices could be the Sistine's first and perhaps the last.
In summit, New Jersey, Lauren Green, Fox News.
Very gusty winds and heavy rain expected through midnight Wednesday morning as a powerful cold front moves in!
After highs Tuesday near 70 degrees, late Tuesday night into Wednesday temps tumble into the 30s and rain changes to wet snow. Little to no accumulation expected.
Freeze warnings posted Tuesday night into Wednesday AM. Protect sensitive plants!