To investigate the clinical and pathological significance of melanin content and cyclin D1 expression in malignant melanoma. Methods: Melanin content and cyclin D1 expression were detected by immunohistochemical staining in one tissue micro-array containing 189 specimens of malignant melanoma between January 2001 and December 2014. Results: There were 76 cases (40.2%) of high melanin content among 189 malignant melanoma patients, and 80 cases (45.7%) of high expression of cyclin D1. The content of melanin was not correlated with the patients＇age, gender, tumor tissue source, and lymph node metastasis, but instead, it was correlated with tumor invasion depth (P=0.001) and clinical stage (P=0.038). The melanin content was much lower in advanced malignant melanoma (stageⅢandⅣor T3 and T4) than in non-advanced melanoma (stageⅠandⅡor T1 and T2). Regarding cyclin D1 expression, there was no significant difference in age, gender, invasion depth (T stage), clinical stage, lymph node metastasis, and tumor tissue source. Melanin content was negatively correlated with cyclin D1 expression in 58 cases of lymph node metastatic malig-nant melanoma (r=-0.271, P=0.039). Conclusions: Melanin content in melanoma tissues may be involved in the invasion, progression, and metastasis of malignant melanoma. The results will provide new evidence for the prognosis and pathological diagnosis of malig-nant melanoma.