Keratinization is a specialized form of apoptosis that produces the stratum corneum concomitant with keratinocyte cell death. Apoptosis of keratinocytes occurs not only during normal keratinization but also in response to various intracellular or extracellular death stimuli, such as genetic defects or UVB. In general, apoptosis is characterized by chromatin condensation, membrane blebbing, cell shrinkage, formation of apoptotic bodies, and deoxyribonucleic acid fragmentation. The nick-end labeling technique is a method to detect DNA fragmentation and is useful to assess the presence of apoptotic cells in tissues or cells. In this chapter, a practical procedure for nick-end labeling using paraffin-embedded sections of skin specimens is described.