This chapter offers a structured, evidence-based clinical approach to assessing oral mucosal conditions, guiding students and clinicians through essential diagnostic steps such as history-taking, visual examination, palpation, adjunctive screening tools, and basic information on biopsy methods. It incorporates decision-making frameworks that differentiate benign, reactive, and potentially malignant lesions. The chapter also emphasises practical strategies for differential diagnosis and interdisciplinary referral, aiming to enhance diagnostic confidence and improve patient outcomes in routine practice.