BackgroundSchinusmolle L. (Anacardiaceae), the Andean “molle” or “mulli,” is among the longest-used trees of western South America. Despite more than 3 decades of pharmacological research, reports remain heterogeneous and no reproducible phytopharmaceutical candidate has emerged—an inconsistency that may arise less from insufficient experimentation than from the biological object never having been adequately defined.AimThis article integrates the historical-linguistic, archaeological, ethnobotanical and taxonomic record and proposes a falsifiable framework—the Mulli Hypothesis—for how the species should be studied. The aim is not to validate the hypothesis, but to establish why the evidence makes it a warranted and testable hypothesis.ArgumentFirst, molle derives from Quechua mulli, a pre-Linnaean vernacular. Second, the most secure ancient evidence is large-scale chicha de molle at the Wari site of Cerro Baúl, corroborated by molle-specific triterpenoid biomarkers. Third, Andean ethnomedicine consistently records external analgesic and anti-inflammatory use of the leaf; modern pharmacology has begun to report activities consistent with this specific observation while also reporting activities the tradition never described. Fourth, nomenclatural instability means the identity of “mulli” is itself unstable, and reported variability may be partly a species-identity artefact and partly a genuine chemotype signal.ProposalHistorical knowledge appears to preserve a reproducible pharmacological signal for a heterogeneous biocultural entity. We propose the ethnopharmacological unit as an operational, falsifiable model underpinning a framework for future standardization. Although developed for molle, the ethnopharmacological unit is proposed as a potentially generalizable analytical approach for investigating irreproducibility where a botanical name may conceal biological, chemical or cultural heterogeneity.