The blast in the Balochistan provincial capital Quetta came as up to 200 people gathered at the Civil Hospital after the fatal shooting of a senior local lawyer, AFP reporters on the scene said.
Video footage showed bodies strewn on the ground, some still smoking, among pools of blood and shattered glass as shocked survivors cried and comforted one another.
Many of the dead appeared to be wearing black suits and ties as a mark of respect for the dead lawyer.
The crowd, mainly lawyers and journalists, had gone to the hospital after the death of the president of the Balochistan Bar Association in a shooting earlier Monday, provincial home secretary Akbar Harifal told AFP.
Bilal Anwar Kasi was targeted by two unidentified gunmen as he left his home for work.
"There at least 45 confirmed dead and around 50 injured," said Rehmat Saleh Baloch, health minister for Balochistan, updating earlier figures.
Officials said mobile phone jammers had been activated around hospitals in the area -- a regular precaution after an attack -- making it hard to contact officers on the ground to get updated information.
There was no immediate claim of responsibility for either the blast or the shooting. But militant groups in the province routinely target security forces and government installations.
Balochistan, which borders Iran and Afghanistan, has major oil and gas resources but is afflicted by Islamist militancy, sectarian violence between Sunni and Shiite Muslims and a separatist insurgency.
The military has been deployed in and around the city's hospitals, Baloch said.
The blast is the second deadliest in Pakistan this year so far, after a bombing in a crowded park in Lahore over Easter killed 75.
Prime Minister Nawaz Sharif condemned the bombing and ordered authorities to tighten security.
"No one will be allowed to disturb peace in the province that has been restored due to countless sacrifices of security forces, police and the people," his statement said.
Facebook activated its safety check for Quetta in the wake of the attack.
Pakistani hospitals have been targeted by militants previously.
In 2010 a bomb killed 13 people outside the casualty department of a hospital in Karachi in Sindh province, where victims of an earlier attack were being treated as anxious relatives gathered.
An overview of the scene of a bomb blast outside a hospital in Quetta, Pakistan. REUTERS
At least 45 people were killed and dozens wounded Monday when an explosion ripped through a crowd of mourners at a hospital in southwest Pakistan, officials said, with fears the toll will rise.
