Simple SummaryFossils are the only direct evidence of life throughout Earth’s history. We examine the biology of ancient animals to learn about evolution and past ecosystems. Biomolecules are a relatively new source of information from fossil records because new technology is now being used in paleontology that makes it possible to detect molecular remains in fossils. However, molecules extracted from fossils are complex mixtures with environmental and other sources of organic compounds. Additionally, macroscale preservation is well-known to vary greatly across fossil localities. Therefore, a goal in molecular paleontology is to develop ways to predict where molecules may be preserved and differentiate between endogenous and exogenous sources. Here, we use a powerful combination of methods that focus on high-resolution mass spectrometry to evaluate the molecular-scale preservation of a dinosaur quarry from the Triassic Period. We found that despite very good overall preservation at this locality, there is no evidence of endogenous molecules, demonstrating that molecular preservation is variable and that good macro- and microscale preservation cannot necessarily be used as predictors for biomolecule preservation in the fossil record.Exceptionally preserved fossils retain soft tissues and often the biomolecules that were present in an animal during its life. The majority of terrestrial vertebrate fossils are not traditionally considered exceptionally preserved, with fossils falling on a spectrum ranging from very well-preserved to poorly preserved when considering completeness, morphology and the presence of microstructures. Within this variability of anatomical preservation, high-quality macro-scale preservation (e.g., articulated skeletons) may not be reflected in molecular-scale preservation (i.e., biomolecules). Excavation of the Hayden Quarry (HQ; Chinle Formation, Ghost Ranch, NM, USA) has resulted in the recovery of thousands of fossilized vertebrate specimens. This has contributed greatly to our knowledge of early dinosaur evolution and paleoenvironmental conditions during the Late Triassic Period (~212 Ma). The number of specimens, completeness of skeletons and fidelity of osteohistological microstructures preserved in the bone all demonstrate the remarkable quality of the fossils preserved at this locality. Because the Hayden Quarry is an excellent example of good preservation in a fluvial environment, we have tested different fossil types (i.e., bone, tooth, coprolite) to examine the molecular preservation and overall taphonomy of the HQ to determine how different scales of preservation vary within a single locality. We used multiple high-resolution mass spectrometry techniques (TOF-SIMS, GC-MS, FT-ICR MS) to compare the fossils to unaltered bone from extant vertebrates, experimentally matured bone, and younger dinosaurian skeletal material from other fluvial environments. FT-ICR MS provides detailed molecular information about complex mixtures, and TOF-SIMS has high elemental spatial sensitivity. Using these techniques, we did not find convincing evidence of a molecular signal that can be confidently interpreted as endogenous, indicating that very good macro- and microscale preservation are not necessarily good predictors of molecular preservation.