IMPORTANCE Mitotic rate is now recognized as having independent prognostic significance in melanoma survival. However, its clinicopathologic associations have not been the focus of any previous study. OBJECTIVE To identify a set of patient and tumor characteristics associated with high-mitotic-rate melanoma with the aim of facilitating the earlier detection of aggressive primary invasive melanoma. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of patients from a multidisciplinary melanoma clinic based in a public hospital. A total of 2397 cases from January 2006 to December 2011 were reviewed by the Victorian Melanoma Service, and 1441 patients with 1500 primary invasive melanomas were included in the study. MAIN OUTCOMES AND MEASURES Mitotic ratewas measured as number of mitoses permm2 and analyzed as ordered categories (0, 1-4 mm: OR, 4.5; 95 CI, 3.2-6.1; >4 mm: OR, 12.6; 95 CI, 7.5-21.1), and ulceration (OR, 2.0; 95 CI, 1.5-2.7). These histopathologic features, along with amelanosis and rate of growth, remained as significant associations with high mitotic rate in the overall multivariate analysis. CONCLUSIONS AND RELEVANCE High-mitotic-rate primary cutaneous melanoma is associated with aggressive histologic features and atypical clinical presentation. It has a predilection for the head and neck region and is more likely to be seen in elderly men with a history of cumulative solar damage who present clinically with rapidly developing disease.