In the Hamadan region, Sanandaj-Sirjan Zone (SaSiZ), W Iran, a pegmatite-aplite vein occurs that contains up to 15 vol% sapphire. The Hamadan sapphire is black to blue, and translucent to opaque, which reveals its semi-gem and gem quality. On the basis of petrographic studies, the Hamadan sapphire-bearing pegmatite-aplite vein represents alkali syenitic to syenitic composition and its adjacent granitoids have a range of composition from syenitic to quartz monzonite and granodiorite. New petrographic, whole-rock geochemical data and δ18O values [9.30–12.45‰VSMOW(Vienna Standard Mean OceanWater)] suggest crustal origin for the peraluminous, S-type and alkaline sapphire-bearing pegmatite-aplite vein. The presence of syngenetic quartz inclusions in the sapphire, and some similar physical-gemological signatures (e.g., parting patterns and angles) of the Hamadan sapphire and kyanite support the generation of the sapphire at the expense of kyanite. In addition, a secondary metasomatic stage may have played a minor role in formation of the sapphire grains. The results indicate an important role for the mafic magmas in triggering crustal anatexis and gem crystallization in continental subduction zone settings.