Proton therapy is an emerging modality for providing radiation treatment to cancer pa-tients. The principal advantages of proton therapy are the reduced total dose deposited into the patient as compared to conventional photon therapy and the finite range of the proton beam. It is considered as a more favorable option for optimum treatment outcomes in terms of maximising tumor control probability and minimising normal tissue complications. The depth dose distribution of the proton beam adds an additional degree of freedom to treat-ment planning. The range in tissue is associated with substantial uncertainties triggered by imaging, patient set-up, beam delivery and dose calculations. Therefore, reduction in uncer-tainties would allow to minimise the treatment volume and thus allow a better usage of the protons. However, the presence of sub-millimeter sized heterogeneities, such is pronounced in trabecular bone and lung parenchyma, in the path of the proton beam can cause the Bragg peak degradation with a widening to the distal fall-o˙. Additionally, the restricted resolution of a classic CT scan used in treatment planning cannot fully resolve such fine structures, potentially leading to inaccuracy in determination of the range.This work aims to investigate the presence of range uncertainties in proton therapy beams when they penetrate through the sub-millimeter sized heterogeneities. The e˙ect of Bragg peak degradation has been demonstrated in bone models with the FLUKA Monte Carlo code and experimental measurements with a 36 MeV proton beam. The bone-substitute material, SAWBONES®, ranging in density from 0.088 to 0.48 g/cc, was used to simulate bone heterogeneities. Micro-CT images were obtained of the SAWBONES® material and used to construct Monte Carlo models of realistic proton radiotherapy treatments and to benchmark experimental studies. Broadening of the Bragg peak and shifts in the range, as defined by the d20% depth-dose parameter were observed both experimentally and in Monte Carlo models, indicating that such e˙ects are in principle, clinically relevant in certain circumstances.Furthermore, a FLUKA Monte Carlo model is benchmarked against the Eclipse treatment planning system (TPS) golden data for proton beam therapy. This project is designed to obtain the proton dose distributions from TPS for a 10 ×10 × 10 cm3 water-filled box. A Monte Carlo analytical model is developed by utilising the information from the TPS to recalculate the dose distribution which are then compared to find any di˙erences (if present) for di˙erent phantom materials. Due to the lack of any experimental information to measure the normalized depth dose as a function of energy, considering the general behaviour of a monitor chamber, it has been assumed that the treatment planning system has a built-in relationship between the monitor units (MU) and dose delivered. A mathematical formula is developed to find the relationship between monitor units (MU) and dose (E). MU α 1/Ea.The value of a is varied from 0 to 1. It has been observed that the beam non-uniformity calculated by using the relationship " MU = E−0.5 " is only 0.15 % for water and 0.43 % for graphite. This non-uniformity in graphite is not severe and it is actually clinically acceptable. This modeling has suggested that the planned dose distributions for water can also be replaced by graphite to a reasonably acceptable standard.