The bombing in Multan signaled a relentless determination on the part of the militants, who - despite being pressured by a major army offensive in one of their Afghan border havens - have sustained a retaliatory campaign since October that has killed more than 400 people. On Monday,in the country killed 59 people.
TV footage from Multan showed several severely damaged buildings in the neighborhood, some with their facades ripped off. Ambulances wailed as security forces flooded the zone, where a Federal Investigation Agency office was also located.
The apparent target of the blast was a building housing an office of Pakistan's most powerful spy agency, Inter-Services Intelligence. Authorities still had not determined how the attack was carried out.
Rizwan Naseer, the official in charge of the area's government-run emergency service, told a Pakistani news channel that the attack killed 12 people and wounded 30 people. It was not immediately clear how many were intelligence agents.
The attack came as U.S. Defense Secretary Robert Gates said Washington was ready to work more closely with Pakistan as soon as Islamabad expressed willingness.
"The more they get attacked internally ... the more open they may be to additional help from us. But we are prepared to expand that relationship at any pace they are prepared to accept," he said.
Early Tuesday, suspected U.S. missiles struck a car carrying three people in the Taliban-riddled North Waziristan tribal region, two intelligence officials said. The region neighbors South Waziristan, the focus of the latest Pakistani army offensive, and is believed to be where many of the Taliban have fled to avoid the military onslaught. The identities of the three were not immediately clear.
All the intelligence officials spoke on condition of anonymity because they were not authorized to speak to the media.
Most of the militant attacks in recent weeks have been directed at security forces, though several have targeted crowded public spaces such as markets, apparently to create public anger and increase pressure on the government to call a halt to the South Waziristan offensive.
"It is obvious the Taliban are seeking to retaliate," a senior Pakistani security official told CBS News' Farhan Bokhari Monday night.
The Taliban generally claim responsibility for attacks on security officers, but not those that kill civilians, though they - or affiliated extremist groups - are suspected in all the strikes.
Late Monday, twin blasts and a resulting fire ripped through the Moon Market, a center in the eastern city of Lahore that is popular with women and sells clothing, shoes and cosmetics. Lahore police chief Pervaiz Lathore said Tuesday that the death toll in the blasts had reached 49, with more than 100 people wounded.
Authorities initially said both bombs at the market were believed to be remote-controlled, but they later said a suicide bomber was suspected to have detonated at least one of them.
Earlier Monday, a suicide bomber killed 10 people outside a courthouse in the northwestern city of Peshawar.
Lahore is Pakistan's second-largest city. It has been hit several times by militants over the past year, including an attack on the visiting Sri Lankan cricket team and several strikes against security installations.
By attacking Lahore and Multan, militants are bringing their war to the heart of Pakistan. Both are cities in Punjab, Pakistan's most populous province, and one far from the northwest regions where al Qaeda and the Taliban have more easily proliferated.
Peshawar has been a more frequent target. The northwestern city lies on the main road into the lawless tribal belt. Of all the attacks since the start of October, the deadliest occurred in Peshawar, where at least 112 people were killed in a bombing at another market.
The rise in militant attacks comes amid growing political turbulence, especially regarding the future of President Asif Ali Zardari, a pro-U.S. leader hugely unpopular here.
On Tuesday, the Supreme Court continued examining the legality of an amnesty protecting him and 8,000 other officials from graft prosecution. The amnesty expired last month, and judges must rule on whether to reopen corruption cases against them.
Although Zardari has immunity from prosecution as president, some experts say the court could now take up cases challenging his eligibility to run for office.