This chapter provides a comprehensive examination of ulcerative oral mucosal lesions, exploring their multifactorial aetiology, clinical presentations, diagnostic approaches, and management strategies. Beginning with the pathophysiological mechanisms underlying mucosal ulceration (trauma, infections, autoimmune conditions, systemic diseases, and neoplasms), the text systematically classifies common ulcerative lesions including aphthous ulcers, herpetic stomatitis, traumatic ulcers, and squamous cell carcinoma. A robust differential diagnosis framework integrates clinical examination, histopathological evaluation, and adjunctive diagnostic tools (viral PCR, immunofluorescence), with case studies illustrating diagnostic decision-making. Special emphasis is placed on distinguishing benign/reactive lesions from malignant conditions, particularly high-risk entities like erythroplakia and oral squamous cell carcinoma. The chapter concludes with emerging technologies (molecular diagnostics, AI-assisted pathology) that are transforming diagnostic paradigms. Throughout, clinical relevance is underscored, particularly the importance of early detection of malignant transformation and evidence-based management protocols.