The melanin affects the pathologic diagnosis, so melanin bleaching must be performed. Our study was to investigate the effect of different melanin-bleaching methods on hematoxylin-eosin staining and immunohistochemical staining. We were used 10 malignant melanoma tissues as experimental subjects, and 3 tissues from T cell lymphoma, B cell lymphoma, neurofibroma and colon as control. Melanin was detected in all 10 malignant melanoma tissues before bleaching. Our study compared among permanganate/oxalic acid treatment, hydrogen peroxide treatment, and double oxidation treatment. The antibodies CD3 and MUM1 negative after potassium permanganate/oxalic acid treatment, but normal expression after hydrogen peroxide treatment. Antibodies CD20 and S-100 can be expressed normally after bleaching. Thus, the 10% hydrogen peroxide for 24 hours at 37°C is the mildest on melanin bleaching, its almost no effect on hematoxylin-eosin staining and immunohistochemical staining. It is suitable for different tissues and antibodies.