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Clinicians have attempted to find early preclinical physical diagnosis signs to detect vascular diseases at the preclinical stage and to prevent clinical deterioration in time. An interesting example of such signs is the Frank sign, which was first described by Dr Sonders T. Frank in 1973. Our goal was to summarize the clinical trials and observational studies that had examined the association between the Frank sign and cardiovascular diseases. Summarizing the 57 studies we found showed that this association could be used for early diagnosis of coronary and vascular diseases in the preclinical stage and that they were found in different populations around the world. Autopsy studies also found a strong association between the Frank sign and cardiovascular causes of death in both sexes. Cardiovascular causes of death included ischemic and hypertensive heart disease, calcific valvular stenosis, ruptured dissecting aneurysm of the thoracic aorta, and ruptured atheromatous aneurysm of the abdominal aorta. The Frank sign was correlated with increased intima-media thickness and stroke and was found in patients with peripheral vascular disease and with cardiovascular risk factors. The Frank sign could serve as a physical sign to help clinicians diagnose cardiovascular diseases.