The missiles struck a fortress-like compound and a vehicle in Ghulam Khan village on the Afghan border early in the morning.
"Some of the militants were on foot. They had just returned from Afghanistan when they were hit," an intelligence official in the region said.
"So far, the death toll is 20."
There was no independent confirmation of the incident as the war zone is located in a remote part of Pakistan. Militant groups often dispute officials' account of such attacks and casualties.
North Waziristan is the main base of Afghan militants fighting Western forces across the border. The United States has stepped up missile strikes there in recent months as it struggles to stabilise war-ravaged Afghanistan.
The United States has long demanded Pakistan launch a military offensive in North Waziristan, but Islamabad is reluctant to do so, and says it needs to consolidate gains made in earlier offensives before opening a new front.
But critics says Pakistan's reluctance stems from its desire to use the Afghan Taliban as bargaining chips in a final settlement with Kabul once foreign forces leave.
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