The unmanned aircraft targeted a Madrassah, a religious school "run by former Afghan Taliban Commander Jalal-u-Din Haqqani", in Dandi Darpakheil, a village near Miranshah, main town of the North Waziristan tribal region.
"There were two drones and they fired three missiles," said a resident of Dandi Darpakheil.
An intelligence official said at least six people had been killed and the death toll could rise.
"Both Uzbeks as well as Arabs were living in the house and adjacent guest house. Six people were killed but we don't know their identity," the official said on condition of anonymity.
The doctors said 15 to 20 wounded people, most of them women and children, had been taken to Miranshah's main hospital.
One of Haqqani's younger sons said his father and son Sirajuddin had been away from the house at the time.
"Haqqani and Sirajuddin were in Afghanistan at the time of the attack. They are alive," Badruddin, the commander's third son, told Reuters by telephone.
Badruddin said one of his aunts had been killed in the attack on the family home. He said six missiles had struck the house, which the family had owned for 30 years.
Military spokesman Major-General Athar Abbas confirmed that an "incident" had taken place in North Waziristan and its cause was being ascertained.
The US-led forces have intensified assaults in the bordering tribal region over the past few weeks killing over 50 people, including women and children.
Last week, the US troops carried out first ground assault in Angoor Adda bordering village, killing more than 20 persons.
Güncelleme Tarihi: 08 Eylül 2008, 13:42