The use of tissue softeners to enhance the quality of tissue sections of heavily keratotic tissue is not widely published. There are very few indicators in the scientific literature that attempt to compare and contrast the benefits and disadvantages of such techniques, as most are passed down through word of mouth rather than through published data. This study attempts to present a preliminary evaluation of several methods employing tissue softeners to facilitate the preparation of reproducible, good-quality formalin-fixed, paraffin-embedded sections of nail tissue. A standard 10-minute surface application of each softener is employed for all paraffin-embedded tissue in order to ensure consistency. The results show that the use of Veet (hair remover), Fairy Liquid or fabric conditioner provides the most beneficial results. Thus, widely available products can be used in preference to specific commercially produced reagents that have no clear benefits and can cost considerably more to purchase. This study will form the basis of a more in-depth evaluation of the most beneficial softeners, in an attempt to determine optimal parameters for their use in routine histopathology laboratories.