Background: Malignant melanoma is the most aggressive form of skin cancer. In contrast to other tumors, the role of estrogen in the initiation and progression of melanoma remains unclear. The aim of this study was to evaluate estrogen receptor beta protein expression in human melanoma tissues and in the benign melanocytic lesions. Method: Twenty-one patients, 11 with cutaneous melanoma and 10 with benign melanocytic lesions were enrolled in this study. Estrogen receptor beta expression in benign melanocytic lesions and melanoma was analyzed by using immunohistochemical staining. Result: All melanocytic lesions expressed estrogen receptor beta protein. We found lower estrogen receptor beta protein levels in melanoma. Conclusion: These initial observations, to be confirmed by further comprehensive studies, could suggest a role for estrogen receptor beta in melanoma, pointing at the possibility of using estrogen receptor beta expression for differentiating between malignant and benign lesions.