Objective: To determine if changes in histologic parameters obtained from intermittent sampling of the entire block correlated with differences in prognosis and management. Design: Prospective analysis of skin biopsy specimens. Setting: Skin pathology laboratory. Patients: One hundred consecutive patients with an unequivocal diagnosis of melanoma. Interventions: Two initial slides were prepared from serial sections of 5-μm thickness. When evaluation of the initial slide revealed melanoma, 5 additional slides were obtained by sectioning at levels through the entire block. Breslow depth, Clark level, ulceration, tumor infiltrating lymphocytes, vascular invasion, regression, presence of a precursor lesion, and histologic type of melanoma for the first slide and the additional 6 slides were analyzed and compared. Results: Review of the additional 6 slides from level sectioning revealed a greater maximum tumor thickness than was evident from the original slide in 43%of the cases. In 10 of these cases, the new maximum tumor thickness measurements changed the surgicalmanagement of the patients. Ulceration was observed in 6%of cases on the initial slides, and an additional 3%of lesions were found to have ulceration on levels. The level of invasion was deeper than originally found in 10%of the cases. Conclusions: Level sectioning through an entire block of a melanoma specimen provides additional information in the classification and management of melanomas. Extensive block sampling will result in more accurate information regarding histologic parameters of melanoma, but the yield must be balanced with the extra cost of materials, time, labor, and the potential disadvantage of not retaining tissue for future use. Design: Prospective analysis of skin biopsy specimens. Patients: One hundred consecutive patients with an unequivocal diagnosis of melanoma. Interventions: Two initial slides were prepared from serial sections of 5-μm thickness. When evaluation of the initial slide revealed melanoma, 5 additional slides were obtained by sectioning at levels through the entire block. Breslow depth, Clark level, ulceration, tumor infiltrating lymphocytes, vascular invasion, regression, presence of a precursor lesion, and histologic type of melanoma for the first slide and the additional 6 slides were analyzed and compared. Results: Review of the additional 6 slides from level sectioning revealed a greater maximum tumor thickness than was evident from the original slide in 43% of the cases. In 10 of these cases, the new maximum tumor thickness measurements changed the surgical management of the patients. Ulceration was observed in 6% of cases on the initial slides, and an additional 3% of lesions were found to have ulceration on levels. The level of invasion deeper than originally found in 10% of the cases. Conclusions: Level sectioning through an entire block of a melanoma specimen provides additional information in the classification and management of melanomas. Extensive block sampling will result in more accurate information regarding histologic parameters of melanoma, but the yield must be balanced with the extra cost of materials, time, labor, and the potential disadvantage of not retaining tissue for future use.