Background: Dose calculation algorithms play a very important role in predicting the explicit dose distribution. We evaluated the percent depth dose (PDD), lateral depth dose profile, and surface dose volume histogram in inhomogeneous media using calculation algorithms and inhomogeneity correction methods. Materials and Methods: The homogeneous and inhomogeneous virtual slab phantoms used in this study were manufactured in the radiation treatment planning system to represent the air, lung, and bone density with planned radiation treatment of 6 MV photons, a field size of 10 × 10 cm2, and a source-to-surface distance of 100 cm. Results: The PDD of air density slab for the Acuros XB (AXB) algorithm was differed by an average of 20% in comparison with other algorithms. Rebuild up occurred in the region below the air density slab (10–10.6 cm) for the AXB algorithm. The lateral dose profiles for the air density slab showed relatively large differences (over 30%) in the field. There were large differences (20.0%–26.1%) at the second homogeneous–inhomogeneous junction (depth of 10 cm) in the field for all calculation methods. The surface dose volume histogram for the pencil beam algorithm showed a response that was approximately 4% lower than that for the AXB algorithm. Conclusion: The dose calculation uncertainties were shown to change at the interface between different densities and in varied densities using the dose calculation methods. In particular, the AXB algorithm showed large differences in and out of the field in inhomogeneous media.