Previous clinical observations have indicated that the metastatic potential for thick malignant melanoma is lower for patients with xeroderma pigmentosum than for other patients. In a prospective study using computerized image analysis to measure the morphometric characteristics of nuclei in these neoplasms, we found that the nuclei of malignant melanoma cells were smaller and more ovoid in patients with xeroderma pigmentosum than in other patients. Objective evaluation and grading of these subtle histopathologic variables could provide a means of establishing prognostic factors unrelated to the thickness of the neoplasm.