In a bid to respond to the diverse needs of individual students such as their unique abilities, interests, learning styles, and cultural backgrounds, lecturers have been using differentiated instruction. Differentiated instruction ensures that all students in the classroom have equitable access to educational opportunities and resources that meet their needs. Despite its goals the implementation of differentiated instruction in higher educational institution is illusive as such this exploratory and qualitative study examined the use of differentiated instruction in the university of Buea one of the most influential higher institutes of learning in Buea Cameroon which provides mentorship to many other higher institution of learning with a focus on courses with enrolment of 30 and above students more. The researcher worked with 35 instructors from four faculties of Education, Science, Social and Management Sciences, and Arts these faculties were selected because the least class size ranged from 30 and above. The findings suggest that differentiated instruction in the university of Buea Cameroon is challenging. Moreover, instructors teaching in the University of Buea need a better understanding of differentiated instructional strategies and how to implement them.