The army, which says it has trapped hundreds of militants and their Pakistani tribal allies in rugged territory near the Afghan border, held fire on Monday to let a delegation of elders talk peace.
However, a convoy heading for the town of Wana to support the operation against the militants was ambushed by fighters with rockets.
"There were 12 dead and 22 wounded," one government official told Reuters. "The army has blocked the road from both ends and no one is allowed to go in."
There was no information on casualties among the attackers.
The battle, involving 5,000 troops, is the biggest Pakistan has ever waged in the tribal area and is part of a major push to try and sweep foreign militants from the Afghan border region and catch al Qaeda chief, Osama bin Laden.
US forces are hunting on the other side of the border. The twin operations come amid heightened world-wide anxiety over al Qaeda attacks.
The fighting in the tribal region of South Waziristan erupted on Tuesday after security forces moved in to hunt al Qaeda suspects and their tribal allies.