The diagnosis of lymphoproliferative and melanocytic skin lesions is one of the most vexing problems in dermatopathology, a problem that is compounded by the far-reaching therapeutic and psychosocial consequences of the diagnosis for both patient and physician. On the occasion of a self-assessment slide seminar held during a dermatopathology meeting, 30 unusual lymphoproliferative and melanocytic lesions, each provided with four differential diagnoses, were evaluated by "expert pathologists" and other participants ("nonexperts") of the slide seminar. The final diagnosis was pinpointed by the majority of the experts in 16 of 30 cases (56%). The group of experts returned an unanimous decision on the diagnosis in only 2 of the 30 cases (7%). In contrast to the expert group, the preferred diagnoses given by the nonexperts showed a wider range. In 20 of 30 cases (66%), the final diagnosis could only be established after consideration of clinical, histologic, immunophenotypic, and molecular features. Our findings agree with the results of recent studies indicating quite a high degree of discordance among expert pathologists. The discordance between experts and, to a higher extent, nonexperts may have some crucial consequences for dermatopathology. Full agreement on diagnosis, particularly in unusual skin lesions, cannot be achieved only by an accumulation of expertises. Instead of relying on one single finding or diagnostic procedure ("gold standard") as the main criterion upon which to base a diagnosis, the diagnoses become more reliable if based on the integration of several factors including an evaluation of clinical and histomorphologic features and immunophenotypic and molecular findings ("diagnostic elements"), particularly in the field of lymphoproliferative and melanocytic lesions. In addition, a continuous retrospective work-up of difficult or unusual cases is recommended to ensure a long-term improvement in diagnostic reliability.