Lesions arising from odontogenic tissues of the jaws vary from very common to very rare. Some, such as radicular cysts, form a routine part of the diagnostic workload for histopathologists who report specimens from the head and neck, but many other lesions are rarely seen and can cause significant diagnostic difficulty for the non-specialist. These issues are compounded by the vagaries of dental disease (and terminology used by dentists and oral surgeons) and issues in the interpretation of radiographic images, which can be crucial to making a correct diagnosis. In this review article, we will discuss a number of areas of diagnostic difficulty, largely based on the authors experience in receiving tertiary referrals. This will focus on practical advice to help avoid the pitfalls in the diagnosis of odontogenic lesions.