Evaluation of cell cycle using antibodies against nuclear proteins involved in regulating DNA replication has gained special interest in the effort to predict biologic behavior of benign and malignant tumors. The aim of this study was to analyze the expression of minichromosome maintenance 2, Ki-67, and geminin in oral nevi and melanomas. Expression of these cell proliferation markers was evaluated by immunohistochemistry in 49 oral melanocytic lesions, including 38 intramucosal nevi and 11 primary oral melanomas. The labeling index of each proliferation marker was assessed considering the percentage of cells expressing nuclear positivity out of the total number of cells, counting 1000 cells per slide. Minichromosome maintenance 2, Ki-67, and geminin were rarely expressed in intramucosal nevi, in contrast to oral melanomas, which showed high levels of these cell proliferation markers, particularly minichromosome maintenance 2, indicating it is a more sensitive marker in primary oral melanomas than Ki-67 and geminin. These results indicate that these markers may be involved in the pathogenesis of oral melanomas and could be eventually useful as an additional diagnostic tool for differential diagnosis of oral benign and malignant melanocytic lesions.