An AFP reporter at the scene saw a building of at least four storeys that had collapsed in the town of Jisr al-Shughur in Idlib, a region controlled by Syria's former Al-Qaeda affiliate.
One opposite had partially caved in while surrounding buildings appeared on the verge of collapse.
A civil defence worker eased himself under a massive slab of fallen concrete to search for victims, as three colleagues crouched by his side to help.
Thirteen civilians were among those killed in the blast, the cause of which was not immediately clear, according to the Syrian Observatory for Human Rights, a Britain-based monitoring group.
"The explosion hit next to the market," killing 15 people including the daughter of a Turkestani fighter, Observatory chief Rami Abdel Rahman said.
He earlier said the explosion could have been the result of a car bomb or a vehicle carrying explosives that detonated.
But bystanders and the head of the local civil defence unit, Abdelwahab al-Abdu, said they did not know what caused it.
Abdu said 13 civilians had died in "an explosion of unknown origin."
Abu Ammar, a father of two, told AFP he felt the "huge" blast from his home about 50 metres away.
"We ran to the place of the explosion and saw the rescue teams trying to pull out the wounded," he said.
There were "people still alive under the rubble, and lots of body parts on the ground."
Rescue personnel were seen directing bulldozers to clear rubble from a road.
Members of the Syrian Civil Defence (White Helmets) search the rubble of a collapsed building following an explosion in the town of Jisr al-Shughur, Idlib, on April 24, 2019. Photo: Omar Haj Kadour/AFP
The Idlib region is under the administrative control of Hayat Tahrir al-Sham (HTS), which is dominated by a faction previously known as Al-Nusra Front before renouncing its ties to Al-Qaeda.
The Turkestan Islamic Party, a group of foreign jihadists from the ethnic Uighur Muslim minority, also has a large presence in Jisr al-Shughur.
The Islamic State jihadist group has sleeper cells in the wider Idlib region.
Idlib has since September been protected from a massive regime offensive by a fragile ceasefire deal signed by Damascus ally Russia and rebel backer Turkey.
But the region of some three million people has come under increasing bombardment since HTS took full control of it in January.
On Tuesday, regime shelling killed seven civilians, including four children, in the town of Khan Sheikhun.
Increased regime shelling on Khan Sheikhun has sparked one of the largest waves of displacement since the September deal.
Syria's war has killed more than 370,000 people and displaced millions since the conflict began with the repression of anti-government protests in 2011.
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