Histologic criteria commonly used to diagnose dysplastic melanocytic nevi (DMN) have not been correlated adequately with biology nor subjected to rigorous reproducibility studies. To address these failings, we developed histologic definitions emphasizing cellular morphology based on the appearance of typical melanocytes in sun-protected buttock skin, fully-evolved atypia in the vertical component of metastasizing primary cutaneous melanomas, and slight and moderate degrees of atypia defined within these limits in selected varieties of DMN. Reproducibility of our histologic definitions were tested by using two pathologists working independently to assess single routine tissue sections of 19 melanocytic lesions on two occasions at least 6 mo apart. Lesions included five previously diagnosed primary invasive cutaneous melanomas, seven lesions selected for gross morphologic features characteristic of DMN, and four solar lentigines and three common acquired nevomelanocytic nevi preselected for typical appearance and stable growth history. For the primary pathologist using the grading scheme, agreement rates between first and second readings were 84% for final diagnosis and 79% for the highest degree of cellular atypia; for the secondary pathologist, agreement rates for first and second readings for both parameters were 84%. Agreement rates comparing second readings of final diagnosis and highest degree of cellular atypia by the two pathologists were 89% and 79%, respectively. Most of the architectural and host response features commonly associated with DMN were less reproducible. In conclusion, we demonstrated very good reproducibility of histologic definitions used to differentiate the intraepidermal component of DMN from that of melanoma and benign melanocytic and nevomelanocytic hyperplasias, based on a biologic correlation emphasizing cellular morphology. Reproducible histologic definitions are a requisite first step in defining a clinical-pathologic correlation for DMN.