They were kidnapped from the village of Mabujeh in Hama province on March 31, said the Syrian Observatory for Human Rights.
News of the kidnap had been kept quiet because of ongoing negotiations for their release, but the talks have since faltered, said Observatory head Rami Abdel Rahman.
Ten of those taken, including six women, are Ismailis, a minority sect that is an offshoot of Shi'a Islam.
The remaining 40 are Sunni Muslims, including at least 15 women.
“There are fears that the women are being taken as slaves,” Abdel Rahman told AFP.
He said the Ismailis were kidnapped because ISIS considers them “infidels,” and that the Sunnis - although from the same sect as ISIS fighters - were taken because ISIS viewed them as “loyal to the Ismailis”.
Mabujeh, east of the provincial capital Hama, has a population of Sunnis, Ismailis, and Alawites, another offshoot of Shi'a Islam that is the sect of President Bashar al-Assad and his clan.
On March 31, ISIS executed at least 37 civilians in Mabujeh, including two children, by “burning, beheading, and firing on them,” the Observatory said.
ISIS has regularly targeted minority sects in Syria, especially Shi'as it accuses of apostasy, as well as Sunnis who it alleges have violated its interpretation of Islam.
It has carried out mass kidnappings of Kurds and Assyrian Christians in Syria, and members of the Yazidi faith in neighboring Iraq.
It is also accused of mass executions of members of minority sects and Sunni Muslims accused who have refused to submit to its rule.