Thousands of Syrians have been evacuated from besieged areas in recent months under deals between President Bashar al-Assad’s government and rebels.
There was no immediate claim of responsibility for the attack, which pro-Damascus media said was carried out by a suicide car bomber.
Rights groups have expressed concern over the mounting civilian death toll, as ISIS fights from homes and densely-populated areas in Mosul.
Syrian warplanes bombarded a besieged rebel-held district of Homs, southern Deraa and insurgent areas in Damascus’s outskirts on Saturday.
The attacks show that even if ISIS loses the Iraqi side of its self-styled caliphate, the threat from the group may not subside.
The truce deal, brokered by Russia and Turkey and welcomed by the UN Security Council, has been repeatedly violated since it began, with warring sides trading the blame.
Monitors reported clashes between insurgents and government forces along the provincial boundary between Idlib and Hama and other isolated incidents.
The options facing those caught up in the rapid government advance are bleak: men of fighting age could be arrested whether they stay put or head to government-held districts. If they flee to rapidly-shrinking rebel-held areas they may only be putting that prospect off.