Purpose: To investigate the clinical reliability of heterogeneity-based dose algorithm using RayStation treatment planning system v.4.0. Methods: The collapsed cone dose calculations in RayStation (RaySearch, Sweden) were compared with the measurements (ion chamber and EBT2 film) and with an in-house Monte Carlo algorithm. A heterogeneous multi-layer phantom and CT images of 4 lung cancer patients were used here. The phantom, composed of multiple solid water slabs and Styrofoams, was irradiated with 6MV beams perpendicular to the layers. The MLC-defined field sizes were 5×5, 10×10, 15×15 and 20×20cm{sup 2}. The chamber was positioned at center of central solid water layer, and the films were placed at interfaces of solid water and Styrofoam. The RayStation dose and Monte Carlo dose were compared by performing absolute gamma analysis (3mm/3%): 1D gamma for PDD in the phantom and 3D gamma for patient volumes receiving dose above 10% of maximum dose. Results: The point dose differences between RayStation and ion chamber measurement were smaller than 1% for all of the field sizes. Between RayStation and film measurement, 5×5cm2 field had the maximum differences : 95% for all the patients. Conclusion: With respect to ion chamber/film measurement and Monte Carlo calculation, the collapsed cone algorithm in RayStation computed reasonable dose in both phantom and patient cases. Heterogeneity-based dose calculation of RayStation is clinically acceptable in heterogeneous media.« less