It is often difficult to predict the outcome of melanoma in patients with Clark level III-IV disease. We sought to identify markers of cell proliferation which may be useful in predicting prognosis. Patients with Clark's level III-IV malignant melanoma who had no local recurrences or metastases were matched with patients of comparable level and thickness who did experience recurrences of metastases. Cell proliferation markers p53, proliferating cell nuclear antigen (PCNA), and Ki-67 were assessed by immunohistochemistry. DNA ploidy was determined by flow cytometry. There was no difference in the expression of p53, PCNA, and Ki-67 between patients with metastases and patients without metastases. However, patients with metastases were more likely to have an aneuploid tumor cell population than were patients without metastases (p < 0.03). Expression of cell proliferation markers do not appear to help predict prognosis in advanced level melanoma; however, aneuploidy may be associated with a greater probability of metastasis.