Proper management of an oral mucosal lesion begins with diagnosis, and the gold standard for diagnosing disease is biopsy. It is important that dental practitioners are aware of normal physiological variations of oral mucosa, as well as macroscopic and microscopic features and distinguish them from pathological changes that can occur on oral mucosa. Biopsy is a medical procedure where a sample of tissue is taken from a living person with the objective of providing a pathologist with a representative specimen for histopathological interpretation and diagnosis. This approach is used for all tissues of the body, including those of the oral cavity, where a wide spectrum of disease processes may occur. When considering biopsy, a little forward planning can greatly improve the diagnostic value obtained. Understanding different biopsy techniques, different tissues and biopsy sites, as well as artefacts that can occur, are crucial for collecting a tissue sample that will be suitable for diagnosis. Inadequate care at any stage could result in a non-diagnostic biopsy and may necessitate the patient having a repeat procedure with its ensuing physical and psychological morbidity. Beside the tissue sample, an accurate clinical description of the lesion can assist the pathologist in the diagnosis; duration, symptoms and changes in appearance, any antecedent events as well as prior diagnostic and therapeutic measures. The location, size, colour, consistency or texture may be facilitated by photography. Regardless who is performing the biopsy, the chosen practitioner still needs to be familiar with the procedure and results obtained so that the patient can be appropriately managed.