Islamic State attacked villages near the only useable road that links the government-controlled cities of Aleppo and Homs on Thursday, killing many residents, Syrian state media and a Britain-based war monitor said.
The Syrian Observatory for Human Rights, said 52 people, civilians and fighters on both sides, had been killed and dozens injured. At least 15 were civilians, including five children, and three of them died in execution-style killings, it said.
State-run SANA news agency said that Islamic State fighters killed 20 people in the village of Aqarib al-Safi - east of Hama city before the army and allied militia repulsed the attack.
The Observatory said Islamic State seized Aqarib al-Safi and parts of the nearby village of al-Mabouja as clashes raged on.
The militants said on social media they had captured Aqarib al-Safi.
In 2015, Islamic State had killed 46 civilians the al-Mabouja village, the Observatory said.
Islamic State has lost recently large swathes of territory in Syria during separate military campaigns, including by the Russian-backed Syrian army and US-backed militias.
The jihadist group still mounts attacks, however, including a swift advance in December to capture Palmyra, which it held for several weeks before the army retook the city.
The army and its allies hold the road and a small strip of land on each side, with Islamic State controlling the eastern area and Syrian rebel groups the west.
The Observatory said Thursday's attack was the most violent so far this year by Islamic State along the road.
Syria's conflict, now in its seventh year, has killed hundreds of thousands of people. The multi-sided war has drawn in global powers, made half the country's population homeless, and allowed ultra-hardline jihadists to expand.