Abstract-This paper, aimed at focusing on polyploidy in mammalian cells with attention to pathology, consists of two parts. The experimental part shows the results of a retrospective morphometric analysis carried out on histological specimens of toxic fatty livers saved together with the inherent records of year 1959. Some polyploid anaphases detected merely by chance and suitable to be quantitated have been analysed by computer-assisted microscopy. The results of this analysis prove that genome amplification may occur even in 16n hepatocytes infiltrated by lipid droplets and, presumably, heavily swollen. This information is relevant to re-interpret correctly pathophysiology of toxic fatty liver. In addition, this paper traces the outline of present knowledge on genome amplification in normal and pathological mammalian cell types. Morphometric data and recent progress of molecular cell biology and genetics are indicative of the importance of ploidy values in connection (i) with differentiation, growth and aging of the normal organism, (ii) with the so-called final differentiation of some cell types, and (iii) with some processes closely linked together, namely, inflammation and repair. Evidence suggests that in the life history of the organism mammal polyploidy is controlled, in the various organs, tissues and cell lines, and/or at different times, by different genetic programs.