Many tools of clinical medicine, such as clinical chemistry and diagnostic imaging, are prioritized for clinical diagnosis over post mortem diagnosis. Indeed, it is reasonable that the assessment of a patient’s functional status should take priority over the post mortem, cross-sectional use of diagnostic tests and laboratory equipment. In addition, these tools are sometimes expensive, and their use does not always have a reasonable cost–benefit ratio. However, some post mortem observations, such as inflammation, pulmonary edema, or infiltration and cerebral swelling, cannot be explained without using immunohistochemical markers for post mortem diagnosis. Introducing blood-based biomarkers into post mortem care could significantly reduce the rates of inconclusive post mortems and discrepancies in autopsy findings and clinical diagnoses. This is particularly relevant in relation to vascular pathology, considering the significant burden that vascular diseases represent for overall mortality. Expanding traditional autopsies with blood-based (circulating) biomarkers to avoid invasive post mortem examination would have cultural, religious, and potentially economic advantages. All of the target molecules were discussed in the context of the processes they up-regulate or down-regulate, which turned out to be the final cause of death. Ultimately, it is evident that further studies are needed to provide concrete validation for using a combination of markers for each case to reach a post mortem diagnosis with or without clinical records.