ObjectivesAn error in the diagnosis of an oral or maxillofacial lesion could potentially be detrimental to a patient’s prognosis and management. Major discrepancies between the initial and subsequent diagnoses of head and neck pathologies range from 7 to 53%. This study determined the rate of discrepancies found in the diagnoses of oral and maxillofacial lesions after a second opinion in Saudi Arabia.MethodsA retrospective single-center study was conducted by oral and maxillofacial pathology consultants to review all cases referred for a second opinion to the oral and maxillofacial pathology laboratory between January 2015 and December 2020. If the second-opinion diagnosis matched the original diagnosis, this was described as “agreement.” If the second-opinion diagnosis did not match the original diagnosis but would not change the management or prognosis of a patient, this was classified as a “minor disagreement.” If the second-opinion diagnosis resulted in the changing of a patient’s management or prognosis, this was categorized as a “major disagreement.” Chi-square test and Fisher’s exact test were used to compare data between original and second-opinion diagnoses. Ap-value of less than 0.05 was considered significant.ResultsOf 138 cases, 59 (43%) had an initial diagnosis and a second-opinion diagnosis that were in major disagreement. The most common tumor for which there was a major disagreement was squamous cell carcinoma. No single factor influenced the occurrence of major disagreements.ConclusionsOur evaluation reiterates the importance of obtaining a second opinion from a specialist in oral and maxillofacial pathology to improve the diagnostic accuracy for lesions. A formal system for this step, in addition to the obtaining of adequate clinical and radiographic information about a patient, is mandatory for the review of difficult cases.Supplementary InformationThe online version contains supplementary material available at10.1186/s12903-023-03085-w.