OBJECTIVES: To critically analyse radiotherapy cost studies published over the last 35 years. METHODS: We conducted a comprehensive and systematic review of the literature searching for radiotherapy cost calculation studies on PubMed (Medline) and Embase databases and in the grey literature. The searches yielded 1327 unique entries that were evaluated against the following selection criteria: actual medical cost, external beam radiotherapy (EBRT), clear description of the cost calculation method. The review for compliance with the criteria was conducted in three phases: title; abstract and then full manuscript. RESULTS: Since 1981, 50 studies satisfied our selection criteria. Any perspective, e.g. societal, institutional, was considered acceptable as long as the institutional resources ‘cost of radiotherapy was presented. Cost assessments of EBRT were conducted within a full economic evaluation framework (5 studies: 2 CEA, 2 CUA, and 1 CBA), cost analysis (24), cost description (18) and investment analysis (3). The scope of the selected studies ranged from comprehensive medical cost of radiotherapy including the department’s overhead (20), to average cost specific to one pathology and/or treatment modality (25) to task-specific costs (7) e.g. shielding. Costs were computed per fraction and/or field (20), per treatment and/or patient (27) and specific to a treatment’s process step (3). Costing methodologies ranged from detailed micro costing (13) to activity-based costing (5) to time-driven activity-based costing (2). Besides these established accounting methods, numerous “home-made” approaches were observed (23) and some studies didn’t state their method (7). CONCLUSIONS: Due to heterogeneity both in methodology, input factors and paucity in costing method’s reporting, it was not possible to compare the cost estimates provided by these various studies. This comprehensive literature review of radiotherapy cost studies highlights the need for such studies to be conducted according to conventional accounting approaches and with rigor in the reporting of cost inputs and methodology.