The blast was the latest in a series of attacks at mosques and Sufi shrines in Pakistan, and underscored the relentless security challenge to a nation where Islamist militants have thrived despite U.S.-supported army offensives against them.
The explosion occurred in Darra Adam Khel, an area near Pakistan's tribal regions where Taliban-led militants have been active. Hundreds of worshippers had gathered at the Sunni mosque Friday afternoon for the most popular prayer session of the week.
The mosque's roof caved in, trapping people in debris. People in private vehicles rushed the wounded to hospitals in Peshawar, the main city in the northwest, TV footage showed. A woman was beating her head, while two elderly men in blood-soaked clothes lay in a hospital corridor.
"The blast tossed me up. I fell down," said Mohammad Usman, 32, a schoolteacher with wounds on his head and arms as he lay on a hospital bed in Peshawar. "Later, it was just like a graveyard."
Haji Razaq Khan, a member of Pakistan's Senate from Darra Adam Khel, says a tribal elder, who had been encouraging people to stand against the Taliban, had a guest room next to the mosque and may have been the target. It was not immediately clear whether that elder, Malik Wali Khan, was among the victims.
Islamist militants have frequently targeted tribal leaders who have taken stands against them.
At least 50 people died, while 80 others were wounded, said Shahid Ullah, a local official.
Provincial Information Minister Mian Iftikhar Hussain called the militants "beasts" that are lashing out at Pakistan's crackdown against them.
"This is part of international terrorism. America, Pakistan and Afghanistan are the main players, who need to work closely and more aggressively to root out this menace," said Hussain, whose only son was killed by militants earlier this year.
Pakistan is in the midst of multiple offensives against Taliban and linked militants in its northwest, including the tribal areas that border Afghanistan.
The U.S. has praised the offensives, in hopes they will break the backs of at least some of the groups involved in attacks on American and NATO troops in Afghanistan. However, Pakistan has yet to mount an operation in North Waziristan, the tribal region where the most dangerous groups working against the U.S. in Afghanistan have bases.
In the meantime, the militants have staged attacks in major cities throughout Pakistan as well as smaller areas. In October, a bomb attack at a Sunni mosque on the outskirts of the main northwest city of Peshawar killed three people and wounded 22. It also occurred during Friday prayers.