The purpose of this study is to compare performance of several dosimetric methods in heterogeneous phantoms irradiated by 6 and 18 MV beams. Monte Carlo (MC) calculations were used, along with two versions of Acuros XB, anisotropic analytical algorithm (AAA), EBT2 film, and MOSkin dosimeters. Percent depth doses (PDD) were calculated and measured in three heterogeneous phantoms. The first two phantoms were a 30 × 30 × 30 cm3 solid-water slab that had an air-gap of 20× 2.5 × 2.35 cm3. The third phantom consisted of 30 × 30 × 5 cm3 solid water slabs, two 30 × 30 × 5 cm3 slabs of lung, and one 30 × 30 × 1 cm3 solid water slab. Acuros XB, AAA, and MC calculations were within 1% in the regions with particle equilibrium. At media interfaces and buildup regions, differences between Acuros XB and MC were in the range of +4.4% to −12.8%. MOSkin and EBT2 measurements agreed to MC calculations within ~ 2.5%, except for the first centimeter of buildup where differences of 4.5% were observed. AAA did not predict the backscatter dose from the high-density heterogeneity. For the third, multilayer lung phantom, 6 MV beam PDDs calculated by all TPS algorithms were within 2% of MC. 18 MV PDDs calculated by two versions of Acuros XB and AAA differed from MC by up to 2.8%, 3.2%, and 6.8%, respectively. MOSkin and EBT2 each differed from MC by up to 2.9% and 2.5% for the 6 MV, and by −3.1% and ~2% for the 18 MV beams. All dosimetric techniques, except AAA, agreed within 3% in the regions with particle equilibrium. Differences between the dosimetric techniques were larger for the 18 MV than the 6 MV beam. MOSkin and EBT2 measurements were in a better agreement with MC than Acuros XB calculations at the interfaces, and they were in a better agreement to each other than to MC. The latter is due to their thinner detection layers compared to MC voxel sizes.