The easiest and cheapest way to analyze the phenotype of most knockout mice is to do a comprehensive necropsy and histopathologic examination of slides of all tissues. Once any lesion is found in a knockout mouse a vast contemporary and traditional literature can be searched for occurrences of similar lesions in other species, including human beings. This may provide further insights into the molecular and cellular pathogenesis of the lesion. In this chapter we will focus on the best way to turn a mouse into a set of slides which can thereafter be studied by investigators and pathologists. Some techniques suggested are not generally used in conventional histology laboratories. Most are decidedly old fashioned. They have all been used successfully in many diverse studies of mice of all ages with all kinds of lesions.