The hairless mouse, whose skin in many ways resembles that of man, is increasing its appearance in the scientific literature, in a variety of fields from dermatology to immunology and cancer research. Due to the fragility of the skin of these animals, special handling is often required to obtain optimal histological results. In processing, embedding and staining, special care must be taken to ensure reproducible slides. Many techniques and stains applicable to human skin are useful on mouse skin; however, differences in skin structure, strength, and in apparent chemical specificities have shown that the methods which are most successful on human tissues are not always the best choices for use on hairless mouse skin. Necessary modifications of standard methods for satisfactory histological processing of whole skin are detailed, in addition to a description of staining techniques found most successful for use on hairless mouse skin.