Pegmatite bodies with a simple mineral composition are widespread within the Sanandaj-Sirjan Zone (SaSiZ), Zagros Orogen, Iran; however, gem-bearing pegmatite bodies are rare. There is a pegmatitic vein within the Hamadan garnet (± andalusite ± staurolite) schist adjacent to the Alvand Plutonic Complex (APC), south of Hamedan city (western Iran), in which large crystals of gem spodumene occur together with quartz, amazonite, beryl, tourmaline, and apatite. This spodumene-bearing pegmatite consists of four major zones with slightly different mineral compositions from the border to the core. The wall zone of quartz-rich granitoid and the intermediate zone of alkali granite have trondhjemitic compositions near the quartzolitic gem-bearing core zone. All parts of the vein are peraluminous in composition and exhibit S-type affinity. Two types of spodumene which have been distinguished in the core zone are colorless to very pale yellow and pink, transparent with vitreous luster and inclusion-free (eye clean) under 10× magnification. The different color in these minerals can be attributed to the slightly different chemical compositions, particularly lower Fe/Mn ratios in the pink material. The δ7Li values of the spodumene (+5.58 to +6.57‰) are indicative of the incorporation of middle continental crustal components in their genesis. Change in the mineral assemblage from tourmaline-bearing in the intermediate zone to spodumene + tourmaline in the core zone of the spodumene-bearing pegmatite is consistent with increasing lithium content from the wall zone to the core. Petrographic, geochemical, and isotopic data indicate that partial melting of middle-crustal Al-rich metapelitic source was followed by fractional crystallization to generate these rocks. In this concern, the required Li for the crystallization of spodumene was probably supplied by the breakdown of staurolite of the Hamadan schist and/or subsequent fractional crystallization of the parent magma. The results also demonstrate that the regional tectonic regime exerts a primary control on the occurrence and emplacement of the miarolitic pegmatite in the upper crust and the formation of gem spodumene during late-stage magmatic activities.