The different town planning cultures that shaped old towns in Anatolia and the Italian Peninsula from antiquity to today are examined as a historical morphological study. The Roman Empire had a great influence on historical towns throughout the territories of Europe, the Middle East and North Africa. The underlying focus of this research is the urban fabric in Anatolian towns, built with similarities to settlements in the Italian Peninsula during the Roman Empire, which have changed with the arrival of different cultures from Anatolian Turks to Ottomans under Islamic influence. Eight fortified Roman origin towns from Anatolia and Italy are selected as samples. The comparison between these towns is based on the time at which they were established and specific elements such as their location and importance in their region and their status in the state to which they belonged. Morphological values and quantitative values are obtained through space syntax analysis. In addition to the comparative analyses, the connection of cultural and religious buildings to the whole town network is examined from a mathematical point of view to understand how cultural alteration influences urban form and structure. The urban tissues in both Anatolian and Italian peninsulas differ in block size and segment length. While the legacy of the Roman Empire still exists in Italy, the influence of Islamic tradition has completely changed the urban pattern in Anatolia. This is also confirmed by mathematical interpretations.