Background: Epistemological beliefs have a pervasive influence on learning and practice. Understanding these beliefs and how they develop, could play an important role in medical student training and shape later clinical practice. Methods: The epistemological beliefs of first-year medical students from an Australian and Malaysian university were explored using a domain-specific instrument. Results: There were significant differences between the disciplinary epistemological beliefs of Australian and Malaysian medical students across many items, and two specific factors (Certainty of Knowledge and Justification for Knowing). Discussion: These findings have potential implications for teaching in biomedical disciplines and adaptation of Western curriculum innovations in Eastern educational contexts. Further work is needed to confirm and understand any epistemological differences and subsequent implications for learning and teaching in medicine.