AbstractA procedure for post‐mortem examination (or necropsy) of mice is provided. The aim is to obtain a “holistic” picture of organs and systems at the anatomical and histological levels. The major issue is tissue preservation, which is achieved by rapid transfer into a fixative solution, usually neutral buffered formalin. Fixation is the first of the four basic steps in histopathological analyses of tissues, which also include embedding, sectioning, and staining. The protocols provided here describe routine methods for tissue fixation, as these methods are integral parts of any necropsy procedure. There is also a Strategic Planning section that addresses the overall approach to histopathological evaluation, as well as specifics such as age and gender of the mice, cohort size, and controls. Curr. Protoc. Mouse Biol. 1:17‐53. © 2011 by John Wiley & Sons, Inc.