A tool used in student-centered education is discussion among students in small learning groups. The Western origin of student-centered education, coupled with cross-cultural differences in communication styles, may detract from its cross-cultural applicability. This study investigates how in student-centered education, students' cultural backgrounds are expressed in discussions and shape students' discussion behaviors and skills. A comparative case study using problem-based learning as a student-centered model was conducted in three medical schools located in East Asia, Western Europe and the Middle East. Four cultural factors were found to potentially cause students, especially those in the non-Western schools, to refrain from speaking up, asking questions, and challenging others in discussions. Six contextual factors mediated the influence of the cultural factors. The findings were incorporated in a conceptual model. The conclusion seems justified that student-centered education is feasible in different cultural contexts, but across these contexts, processes and outcomes are likely to differ.