The last diagnosis: why cause-of-death attribution needs a diagnostic framework

The cause of death is medicine's last diagnosis, but it is not supported by the same type of explicit diagnostic architecture that exists for many complex clinical conditions. International mortality systems standardize certification, coding and statistical comparability, yet they do not provide a general architecture for deciding whether a lesion, toxin, genotype, physiological event or circumstance was lethal in an individual case. This distinction matters for clinical genetics, family prevention, public-health surveillance, research reproducibility and legal proceedings. This Perspective argues for an upstream diagnostic layer between autopsy and International Classification of Diseases (ICD): a positive diagnostic architecture for cause-of-death attribution — one that defines how evidence is integrated into a causal diagnosis. Such a system would not replace ICD, death certificates or specialist guidelines. Rather, it would define diagnostic entities, entity-specific criteria where appropriate, exclusion criteria, minimum investigations, levels of certainty and standards for validation. The goal is not a literal “DSM of death”, but an evidence-based architecture that makes causal attribution transparent, reproducible and empirically testable.