Abstract Annotations in Pomponio Leto’s manuscript of Lucretius (now in Naples) reveal patterns in his engagement with the text, especially a focus on rare grammatical forms, participles, adverbs, time, and technical vocabulary usable for scientific, medical, and ontological discussion. Leto and fellow scholars of the studia humanitatis undertook an ambitious linguistic intervention, attempting to create a new classicizing Latin, which rejected simplified Medieval forms and adhered strictly to classical models. This led humanists to seek out everything rare, irregular, and absent from Medieval texts, and often to overshoot their ancient models in complexity, composing hyper-ornamented Latin no native speaker would produce. Thus negative space – all that was unknown, rare, and obscure in rediscovered classics – stands alongside Cicero and Virgil as a major shaper of Renaissance Latin style. The determination of humanists to reject scholastic Latin also meant rejecting the corpus of useful technical vocabulary developed in preceding centuries for discussions of such topics as cognition, perception, ontology, and cosmology. To rival the scholastics, humanists like Leto needed to develop a classical technical lexicon capable of discussing such topics with rigor. Leto’s annotations show how, while searching this newly rediscovered text, he was striving to (re)construct a classical Latin technical lexicon which we might say never existed.