Introduction Polymer gel dosimeters offer a practical solution to 3D dose verification for conventional radiotherapy as well as intensity-modulated and stereotactic radiotherapy. In this study, EGSnrc calculated and PAGAT polymer gel dosimeter measured dose profiles from single shot irradiation with 18 mm collimator of Gamma Knife in homogeneous and inhomogeneous phantoms were compared with each other. Materials and Methods The head phantom was a custom-built 16 cm diameter plexiglas sphere. Inside the phantom, there were two cubic cutouts for inserting the gel vials and inhomogeneities. Following irradiation with the Gamma Knife unit, the polymer gel dosimeters were scanned with a 1.5 T MRI scanner. For the purpose of simulation the simplified channel of 60Co source of Gamma Knife BEAMnrc and for extracting the 3D dose distribution in the phantom, DOSXYZnrc codes were used. Results Within high isodose levels (>80%), there are dose differences higher than 7%, especially between air inserted and PTFE inserted phantoms, which were obtained using both simulation and experiment. This means that these values exceed the acceptance criterion of conformal radiotherapy and stereotactic radiosurgery (i.e., within some isodose levels, less than 93% of prescription dose are delivered to the target). Conclusion The discrepancies observed between the results obtained from heterogeneous and homogeneous phantoms suggest that Leksell Gamma Knife planning system (LGP) predictions which assume the target as a homogeneous material must be corrected in order to take care of the air- and bone-tissue inhomogeneities.