The pope spoke with Kate and Gerry McCann as he greeted dignitaries seated in the front row during his weekly general audience in St. Peter's Square.
"He was very kind, very sincere," Kate McCann told a packed news conference later. She said Benedict assured them that he would continue to pray for Madeleine's safe return.
"It was more personal than I ever could have imagined," said Gerry McCann. He said Benedict immediately recognized Madeleine's photograph.
"His touch and thoughts and words were more tender than we could have hoped and that will sustain us during this most difficult time," he said.
The Vatican had readily accepted the British couple's request to meet with the pope. CBS News correspondent Allen Pizzey reports that their audience with the pontiff was the latest effort by the McCann's to raise awareness of the case.
The McCann's, Roman Catholics, recently prayed at the pilgrimage site in Fatima, Portugal, for her safe return.
The couple also outlined plans in the search for their daughter, saying they would go to Spain, Germany and the Netherlands — countries that send many tourists to holiday resorts in Portugal.
Her picture has been circulated throughout Europe, a campaign that her parents say has helped them cope, reports Pizzey.
Gerry McCann brought a poster of his missing daughter, which has been widely distributed, to the news conference at the residence of the British ambassador to the Vatican. He said the family was asking people going on vacation to put up the posters to further publicize the disappearance.
He said he was grateful for the outpouring of solidarity.
"One evil act seems to be generating so much good," he said.
"Obviously we have very mixed emotions about being here, and of course why we are here." Gerry McCann said as he arrived in St. Peter's Square. "In normal circumstances it would be one of the most exciting things we could do in our own lifetimes, but very much on our minds is the fact that we are here without Madeleine."
A Vatican spokesman, the Rev. Ciro Benedettini, said British Cardinal Cormac Murphy-O'Connor had requested the McCann's meeting with the pope.
"We are talking about a family drama that has touched world public opinion. It could not but touch the Holy Father, especially since these people are Catholics," Benedettini said.
Madeleine McCann disappeared May 3 when her parents left her and her 2-year-old twin siblings alone in their hotel room while they went to a restaurant in their hotel complex in Praia da Luz, a resort town in Portugal's Algarve region. Gerry and Kate McCann have said they will not return to Britain without their daughter.
"We have no plans to go back to the U.K. at the moment. I can't even think about that now, to be honest," she said.