Immunohistochemical staining on paraffin sections for S-100 protein improved diagnostic accuracy for melanocytic tumor. But specificity of S-100 protein in the diagnosis of melanocytic tumor is very low, because S-100 protein was also expressed in neurogenic tumor and salivary gland tumor. To investigate a specific tumor marker for the malignant melanoma, immunohistochemical staining for HMB-45 and S-100 protein was performed on the paraffin sections of 25 cases of malignant melanoma and 46 cases of nevi. Positive reaction for HMB-45 and S-100 protein was diffusely identified in the cytoplasm of tumor cells. Positive ratio for HMB-45 was 100% in malignant melanoma, 92% in junctional component of compound nevus and 0% in intradermal nevus. Positive ratio for S-100 protein was 92% in malignant melanoma, 100% in compound nevus and 100% in intradermal nevus. The sensitivity and specificity for HMB-45 in malignant melanoma were 100%, but those for S-100 protein were 92% in sensitivity and 86.7% in specificity. These results indicate that HMB-45 has a high sensitivity and specificity for malignant melanoma cells and it can be quite useful for the histopathological diagnosis of malignant melanoma.