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Clemson Montessori School, Inc. was founded in 1976 as Alpha Montessori School, a non-profit parent cooperative, by a small group of parents who saw the need for a school that nurtured the whole child. The school began with 17 preschoolers and a young teacher in a single room in the basement of the First Baptist Church of Clemson.

After a few years, Alpha Montessori relocated to its present location on Pendleton Road. In 1988 the school was incorporated and became a privately owned, for-profit school. Over the years, the school grew from a preschool housed in one building to a school for students 2.5 through 6th grade with five buildings on campus. The Montessori Teacher Training Institute (MTTI) was also established at CMS in 1995 and served as a Montessori Teacher Education Program through 2014.