In Traditional Chinese medicine, auricular reflexogenic areas are used extensively in diagnosis and therapy. The diagonal crease of the ear lobe, was rediscovered by Frank in 1973, in association with cardiovascular diseases. Over the years, the question if this sign is genetically determined or not still stands. Earlobe creases have an autosomal dominant inheritance, with FOXP1 and SCN1A genes identified as being related to them. An association between C-3-F gene, FS and essential hypertension with atherosclerosis was identified. The occurrence of FS is believed to be due to early degeneration of elastin and unbalanced ratio of collagen to elastin, traits that reflect microvascular disease, with similar results observed in the earlobes and the coronary bed. Purpose: to assess the role of Frank’s sign presence/absence and expression in the screening of preclinical myocardial autonomic ischemic disorders based on the periodontitis-organ(heart)-target concept. There were enrolled 250 patients with various conditions (atherosclerosis, diabetes, paroxysmal states, periodontitis, orofacial pain) and 250 healthy individuals. The FS presence was assessed clinically, in correlation with the presence of preclinical myocardial autonomic ischemic disorders (PMAID). PMAID was identified using the Myocardial Index, based on ECG dispersion mapping method (CardioVisor-06s). FS was present in 29.6% cases of subjects with PMAID (Myocardial Index >18%), 8.9% cases in non-PMAID individuals (Myocardial Index <18%; p < 0,001); healthy non-PMAID subjects - 7.1%. FS expression is higher in PMAID subjects (p < 0,001). Age correlates strongly with MAID expression, but insignificantly with FS expression. Frank’s sign is an important landmark that may be used for screening signs of preclinical myocardial autonomic ischemic disorders (sensitivity – 71.6%, specificity – 69.9%). Apart from the genetic aspect, we comprehensively analyze the obtained results also in regard to other hypotheses: 1) reflexogenic; 2) atherosclerosis marker; 3) ageing sign; 4) a mechanical result due to sleeping pattern. Our experience demonstrates that presence of Frank’s sign requires a multidisciplinary approach in screening of preclinical myocardial autonomic ischemic disorders.