Iran with an area of 1.648 million km(2) is located between the Caspian Sea and the Persian Gulf. The Iranian population consists of multiethnic groups that have been influenced by various invasions and migration throughout history. Studies have revealed the presence of more than 47 different β-globin gene mutations responsible for β-Thalassemia in Iran. This paper is an attempt to study the origin of β-Thalassemia mutations in different parts of Iran. Distribution of β-Thalassemia mutations in Iran shows different patterns in different areas. β-Thalassemia mutations have been a reflection of people and area in correlation with migration and origin of ancestors. We compared the frequencies of β-globin mutations in different regions of Iran with those derived from neighboring countries. The analysis provided evidence of complementary information about the genetic admixture and migration of some mutations, as well as the remarkable genetic classification of the Iranian people and ethnic groups.