Melanosis is a normal condition found in many mammalian species where there is deposition of melanin pigment in various organs. This presents as rather spectacular black and brown spots of irregular shape. In mice, the most commonly affected organ seen at the time of necropsy is the spleen. Part or all of the spleen may be heavily pigmented. Microscopically, the pigment is darker than hemosiderin and affected cells have a characteristic elongated appearance. The melanin can be differentiated from hemosiderin with a Prussian blue stain. Melanin remains dark brown while iron-based hemosiderin turns blue. In our experience, this feature is limited to various strains of black mice.