Background: The proliferative activity of some tumors is related to the development of metastatic disease and survival. Thus it could be used as a potential prognostic variable. Objective: The purpose of this study was to determine the prognostic value of the Ki-67 index and of a “proliferation-based prognostic index” (PBPI, derived as tumor thickness × Ki-67 index/100) in localized cutaneous malignant melanoma (CMM). Methods: The Ki-67 index (percent of total tumor nuclei) was determined in a series of 84 localized CMMs, with the use of the alkaline phosphatase-antialkaline phosphatase labeling method in formalin-fixed, paraffin-embedded material, and was correlated with other prognostic variables. Survival analysis was performed to determine whether the Ki-67 index and the PBPI could be predictive of metastatic spread or recurrent disease. A stratified analysis of these two parameters according to the tumor thickness was done. Results: An association among the Ki-67 index and location, Clark level, tumor thickness and stage, and prognostic index was detected. Increased Ki-67 index and PBPI were associated with poorer overall survival (P = .03 and P < .0001, respectively) and disease-free survival (P = .01 and P < .0001, respectively). However, after stratification for thickness, only the PBPI showed independent prognostic significance, restricted to tumors thicker than 4 mm (P = .03). Conclusion: The determination of the PBPI in CMM conveys prognostic information for localized thick (>4 mm) CMM, identifying two groups of patients with distinct outcome. (J Am Acad Dermatol 2000;43:991-1000.)