Computer-based calculations were used to simulate the mass spectra for a number of uniform macromolecules having fixed, well-defined chain lengths. The presence of naturally occurring carbon, hydrogen, oxygen, and halogen isotopes introduced significant levels of mass heterogeneity into these systems. For a given polymer, mass variability was demonstrated to be a function of both the elemental composition and degree of polmerization of the polymer chain. In many cases, these natural variations in mass exceeded the molecular weight of one or more monomeric repeat units along the polymer backbone, effectively blurring the mass distinction between uniform polymer constructs formed from N and N+1 repeat units, The significance of isotopic diversity and its potential impact on the synthesis and physiochemical properties of highly uniform macromolecules is also discussed.