The missile hit a house on the outskirts of Miranshah, the main town in North Waziristan, a local official said, in the fourth such strike in a week aimed at Taliban or Al-Qaeda fighters hiding out in the rugged tribal area.
"The pre-dawn strike destroyed the house and 12 people were killed," the official told AFP, adding that another 14 people were wounded.
The 12 were believed to be rebel fighters, locals said, adding that the house hit in the Tol Khel area had been rented by an Afghan militant organisation, Al Badar, and was being used as an office.
Al Badar, backed by former guerrilla leader Gulbuddin Hekmatyar, has previously conducted operations against Afghan and international forces based across the border in Afghanistan, residents and a security official said.
Hekmatyar was briefly prime minister of Afghanistan in the 1990s after the end of its Soviet occupation.
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He has backed the Taliban since the regime was removed from power following the US-led invasion of the c