Background: Dermatologists have expertise in the clinical diagnosis of benign melanocytic nevi. However, there are no data to confirm the accuracy of diagnosis. Differences in the diagnostic accuracy between dermatologists and nondermatologists with regard to cutaneous tumors has been infrequently studied. Objective: We examined the rate of malignant tumors occurring in lesions submitted for routine microscopic examination that were clinically diagnosed as benign melanocytic nevi. Methods: We conducted a study at a regional, non-hospital-based dermatopathology laboratory using specimens submitted by physicians of various specialties who were practicing in a 5-state Midwest region of the United States. The preoperative and postoperative diagnoses were examined on the basis of information provided by the clinician and of the subsequent histopathologic diagnosis. A total of 7734 cutaneous pathology reports were reviewed. Specimens submitted with a preoperative clinical diagnosis of mole or nevus, with or without a modifier, were examined and compared with postoperative microscopic diagnoses. Results: Of 1946 specimens clinically diagnosed and submitted as benign nevi, 45 (2.3%) were histologically diagnosed as malignant tumors. This included 12 melanomas, 30 basal cell carcinomas, and 3 squamous cell carcinomas. For specimens submitted by dermatologists, the rate of malignant tumors increased when clinical information suggested findings beyond the classic benign clinical presentation with the addition of modifiers such as irritated or atypical, or if a malignancy was considered in the differential diagnosis (trend for increasing clinical suspicion: P = .00002). Fewer dermatologists than nondermatologists mistook a malignant tumor for a benign nevus (1.3% vs 3.8%, P = .003). Conclusion: Our data document that 2.3% of clinically diagnosed benign nevi were microscopically diagnosed as malignant tumors. Whether this malignancy rate in clinically diagnosed, benign, melanocytic nevi is above or below the threshold to establish a policy for submission for histopathologic examination remains to be determined as a collective societal and medical professional responsibility. (J Am Acad Dermatol 1999;40:567-71.)