The blast, in the Azaz district of greater Aleppo province, occurred Thursday near the rebel-controlled Bab al-Salam border crossing with Turkey, the Syrian Observatory for Human Rights reported.
The dead included 14 Syrian rebels, and the number of critically wounded could mean more fatalities, according to SOHR.
Video from the border crossing showed a chaotic scene near a charred SUV as paramedics tended to the wounded and loaded covered bodies onto ambulances. A crying man, his hands on his head, moved through the crowd.
The attack comes one week after at least 29 Syrian rebels were killed in a suicide attack against their position on the Syrian-Turkish border, according to SOHR.
Last week's explosion occurred as rebels switched shifts at a position at the Atama border crossing, which is controlled by the Ankara-backed Free Syrian Army, SOHR reported.
ISIS' media wing, AMAQ, claimed responsibility for that attack via Twitter.
Though no claim of responsibility for the latest assault has been made, ISIS has increased attacks on the border since Turkey launched Operation Euphrates Shield in late August.
Turkey said it launched the military campaign to improve security and clear the Sunni terror group from the border region.
Syria's neighbor said it was pressed into action against ISIS by the surge of suicide attacks in Turkey, as well as the terror group's use of safe houses and "informal" financial services on Turkish soil.
The military intervention in northern Syria was intended to target terror groups that Turkey said "threaten the country," a reference not only to ISIS but also pro-separatist Kurdish fighters who are also battling the terror group.
Turkey views both ISIS and Kurdish rebels as foes and its allegiances have complicated its relationship with the United States.
Kurdish fighters have been a key ally of the United States in the war against ISIS in Syria and Iraq, but the Turkish government views those fighters -- the People's Protection Units in Syria, also known as the YPG -- as an affiliate of the Kurdistan Workers' Party, a pro-separatist group that Turkey has been fighting for years.