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Background Few studies have compared patient and anatomic characteristics across the broad scope of oral and maxillofacial disease seen in dental clinics. The authors conducted a study to make these comparisons by surveying a large sample of histologically diagnosed oral and maxillofacial lesions in a US adult population. Methods A total of 51,781 specimens biopsied from 51,781 adult patients were received by an oral pathology service over 13 years (2001-2015) and analyzed. A description of patients’ sex and age at diagnosis, as well as the anatomic site of biopsy was given for diagnoses of 10 oral disease types, including malignant neoplasm, benign neoplasm, infectious, reactive, potentially malignant, developmental, healthy tissue, immune dysfunction, physical trauma, and other. Results The authors reported reactive lesions were the most prevalent disease type found in the sample (74.9%). Malignant diagnoses comprised 1.97% of all biopsies. The 3 most prevalent diagnoses in this study included benign keratosis, chronic apical periodontitis, and radicular cyst. Different anatomic sites, patient age groups, and sexes show different distributions of disease. Conclusions Certain disease types and diagnoses were found to have a higher prevalence by sex, among particular age groups, and in certain anatomic sites. Practical Implications This information provides clinicians with a detailed and broad scope of the variety of oral and maxillofacial lesions processed at an oral pathology service and may assist practitioners in forming clinical impressions and differential diagnoses.