The increasing production and use of fullerene nanomaterials has led to calls for more information regarding the potential impacts that releases of these materials may have on human and environmental health. Fullerene nanomaterials, which are comprised of both fullerenes and surface-functionalized fullerenes, are used in electronic, optic, medical, and cosmetic applications. Measuring fullerene nanomaterial concentrations in natural environments is difficult because they exhibit a duality of physical and chemical characteristics astheytransition from hydrophobic to polar forms upon exposure to water. In aqueous environments, this is expressed as their tendency to initially (i) self-assemble into aggregates of appreciable size and hydrophobicity, and subsequently (ii) interact with the surrounding water molecules and other chemical constituents in natural environments thereby acquiring negative surface charge. Fullerene nanomaterials may therefore deceive the application of any single analytical method that is applied with the assumption that fullerenes have but one defining characteristic (e.g., hydrophobicity). Our findings include the following: (1) Analytical procedures are needed to account for the potentially transitory nature of fullerenes in natural environments through the use of approaches that provide chemically explicit information including molecular weight and the number and identity of surface functional groups. (2) Sensitive and mass-selective detection, such as that offered by mass spectrometry when combined with optimized extraction procedures, offers the greatest potential to achieve this goal. (3) Significant improvements in analytical rigor would result from an increased availability of well characterized authentic standards, reference materials, and isotopically labeled internal standards. Finally, the benefits of quantitative and validated analytical methods for advancing the knowledge on fullerene occurrence, fate, and behavior are indicated.