A skin sample from the Iceman (Otzi, Similaun Man, Man from Hauslabjoch) was studied by means of IR spectroscopy and histology, and the results were compared to those obtained from nine other more recent human tissue samples with known case reports. Attenuated total reflection IR spectroscopy was used for studying the fate of proteins and lipids in these rare skin tissues. This technique provided a simple yet powerful means for semiquantitative determination of the main compound classes found in skin samples, namely, triacylglycerols, their main breakdown products (fatty acids), and proteins. When combined with histology, IR spectroscopy provided reliable information about the main conditions under which mummification of the samples had taken place. In the case of the 5300-year-old Iceman, preserved collagen contributed to the conservation and morphological structures of the skin, although no cellular structures such as nuclei survived. In addition, post-mortal alterations such as hydrolysis of triacylglycerols and phospholipids into fatty acids were unequivocally demonstrated. The solidified fatty acids provided a certain degree of preservation to the tissue characteristic of adipocere. Based on this observation, taken together with the concomitant loss of epidermis, we suggest that Iceman’s body was submerged in water for a period of at least several months prior to desiccation. Results from other research disciplines support our conclusions.