Certified reference materials (CRMs) play a critical role in validating the accuracy of nutrient data for food samples. A number of available food CRMs of differing matrix composition have assigned concentrations for various nutrients, along with associated uncertainty intervals (UIs) for those values. These CRMs have been used extensively in the United States Department of Agriculture’s (USDA) ongoing National Food and Nutrient Analysis Program (NFNAP) to monitor the accuracy of assays of key foods and nutrients consumed in the United States. A total of 690 assigned values for individual nutrients, including proximates, vitamins, macroelements, microelements, fatty acids, amino acids, and selected phytochemicals (e.g., carotenoids), were compiled from the certificates of analysis for 63 CRMs, and the specified UI in each case was expressed as a percentage of the assigned certified or reference concentration. Across all nutrients, 63.5% of the UIs were less than 10% of the assigned value, 25.5% were 10–20%, and 11% were greater than 20% of the assigned value. The UIs for proximates, minerals, and trace elements were most consistently less than 10% of the assigned value. The relative uncertainties were significantly higher for vitamins, suggesting greater challenges in measuring and certifying these components. These high UIs (greater than 10% assigned value) in the best available reference materials are likely to be indicative of the precision and accuracy that can be obtained by current measurement systems for these components. These data suggest that care must be taken in choosing CRMs to monitor food composition analysis, including evaluating what levels of uncertainty are required in assigned values and which analytical measurement systems for food components need closer examination and improvement.