Background: The proliferative activity of melanoma cells, evaluated as MIB-1 immunoreactivity against a Ki-67 epitope, has been considered an indicator of poor prognosis in thick primary melanomas. Objective: The aim of the study was to assess the correlation between the growth fraction of primary melanomas, assessed by means of Ki-67 immunoreactivity, and metastatic relapse. Methods: Ki-67 reactivity in primary melanomas was evaluated as at least 5% of positive neoplastic cells and was assessed on fresh specimens of 55 primary lesions at the time of excision. Such reactivity was correlated with metastatic relapse of patients in a prospective study, by means of multivariate Cox regression models (follow-up, 3-120 months). Results: Ki-67 immunoreactivity was associated with increasing thickness (P = .003). Positive correlation was found between Ki-67 reactivity and metastatic dissemination in primary melanomas less than 1.5 mm thick (n = 23; mean thickness, 0.75 ± 0.3 mm; P = .002). On the contrary, a negative correlation was found between Ki-67 reactivity and metastatic activity in primary melanomas thicker than 1.5 mm (n = 32; mean thickness, 4.0 ± 1.6 mm; P = .019). Conclusion: Ki-67 proliferative activity appears to be a possible predictor of metastasis in primary melanomas, in particular, an indicator of poor prognosis in lesions less than 1.5 mm thick. (J Am Acad Dermatol 2001;44:188-92.)