"It happened close to the border," a Pakistani military officer said.
"We have reports of 10 dead but it will take time to get more information."
The North Waziristan region is a reputed stronghold of the Taliban and al-Qaeda linked fighters.
Other Pakistani officials told the AFP news agency that up to 14 fighters were killed when the missile strike destroyed an al-Qaeda training camp.
Four missiles
Four missiles are thought to have been fired at the camp, in Kum Sham village, some 35km south of Miranshah in North Waziristan.
Security sources said the village is dominated by Wazir tribes and is near the border with South Waziristan, another hub of Taliban and Al-Qaeda operatives.
"Between 11 to 14 militants, mainly foreigners, were killed in the strike," a senior military official said.
It was not immediately clear if there were any high-value targets among those killed, sources said.
An intelligence official, also speaking on condition of anonymity, said: "The strike successfully destroyed the camp."
Al Jazeera's Kamal Hyder, speaking from the Pakistani capital Islamabad, said: "At the moment we are being told by sources in the area that the attack took place in the Razmak village [of North Waziristan].
"We are told that up to 17 people were also wounded in this attack.
"Just a few days ago we were in this region. And we were able to observe that even at nighttime the drones have been flying over this area.
"It has also causing considerable anger in that region because the Pakistani military forces have been deployed in very large numbers along this border and every time there is a strike deep into Pakistan it creates more public resentment. Not just against the Americans but also the local forces which are not able to stop these attacks.
"In spite of opposition by the Pakistani government, the Americans have been buzzing the Pakistani tribal territories ... and they have been picking out targets with impunity."
Sovereignity violated
At least 18 such attacks by unmanned US aircraft have occured since September.
However, this is the first since General David Petraeus, the US Central Command chief, took charge of the war in Afghanistan.
Petraeus told The Associated Press in an interview in Afghanistan on Thursday that the strikes had killed three "extremist leaders" in recent months.
Pakistan has objected to the attacks as a violation of its sovereignty.
The Pakistan army is embroiled in an offensive against fighters in Bajaur, another part of the border region, and is trying to persuade local tribes to join the fight.
Pakistani helicopters and jets killed 17 suspected fighters and wounded 10 others in Bajaur late on Thursday, Jamil Khan, the number two government representative in the semi-autonomous area, said.
Suicide attacks
Hours earlier, two suicide attacks targeting pro-government tribesmen and security forces killed at least 19 people and wounded dozens more.
One of them struck in Bajaur, killing 17 pro-government Salarzai tribesmen who had formed a militia to combat the Pakistani Taliban.
Forty other people were hurt, officials said.
In the nearby Swat walley, a suicide car bomber rammed his vehicle into a checkpoint near a police compound, killing at least two paramilitary troops and wounding 20 other people, officials said.