Abstract: Introduction: The geographical distribution of Behcet's Disease (B.D) is thought to be due to the predisposing factor(s) spread along the Silk Route. It is widely accepted that the predisposing factor(s) is of genetic origin. However the rarity of BD among Hawaiian's Japanese immigrants may be in favor of environmental factors. Iran is situated in the middle of the Silk Route. Caucasians account for 75.4%, Turks (from Mongoloid ethnic origin) for 22%, and Semites for 2.6% of the population. The first study done in Iran was on 1065 patients and in 1992. It was presented to the 7th APLAR congress of Rheumatology. It showed an increase in the incidence of the disease among Turks. An increase in the incident of the disease, in the same geographical area, in a particular ethnic group was in favor of the genetic predisposition of the disease. It showed that the genetic background was derived from the Mongoloid race. BD was spread to the Middle East countries by the invasion of Turks in the 10 th and then the 12 th century. The present study was undertaken on 3024 patients, all of Iranian origin, to verify the conclusions obtained from our precedent study. Materials and Methods: The selection of cases was on consecutive patients. The ethnic origin, the region of birth, and the region of residence were assessed. An adjustment factor was applied to the data for the comparison of results. The adjustment factor was calculated in two different ways. The first adjustment was to bring down to the same level the prevalence of each ethnic group in the country. The second adjustment factor was to counterbalance for the patients the difficulty of access to the Center (financial and distance) from different regions. A confidence interval (CI) at 95% was calculated for the percentages. Percentages were compared with the Standard Error of Difference between Percentages (SE diff%). Results: The number of patients in the 3 main ethnic groups was: Caucasians 1920 (63.6%), Turks 1081 (35.6%), and Semites 23 (0.8%). After application of the first adjustment factor, the adjustment percentages became 30.5% (CI: +1.6) for Caucasians, 58.9% (+1.8) for Turks, and 10.6% (+12) for Semites. The SE diff% between Caucasians and Turks was 1.23 (p<0.0001). It was 1.06 between Semites and Turks (p< 0.0001). After the second adjustment, the adjusted percentages became 25.1% (+1.5) for Caucasians, 52.8% (+1.8) for Turks, and 22.1% (+1.6) for Semites. The SE diff% (Caucasians/Turks) was 1.20 (p<0.0001). It was 1.18 between Semites and Turks (p<0.0001). Discussion: The difference between Turks in one side, Caucasians and Semites on the other side was statistically significant with both adjustment methods. No pure Caucasian was detected among BD patients (no Zoroastrians). It was concluded that the origin of the genetic factor was from the Turkic tribes coming from the northern part of China.