The aim of this study was to develop a framework in which the cost-effectiveness of new imaging technologies could be evaluated using data from other countries, while assessing the impact that any differences between the study populations and Australia may have upon the results. Publications reporting the cost-effectiveness or therapeutic impact of positron emission tomography (PET) were re-worked using Australian cost structures. PET was assigned a cost of $950. The effects of potential differences between the populations studied and the Australian population were evaluated by applying sensitivity analysis to those publications that describe decision tree methodology. The parameters included in the sensitivity analysis were disease prevalence and specificity of PET. The Australian cost savings per patient examined by PET were $505.50-$912.41 for investigation of solitary pulmonary nodules, $34.65-$360.03 for lung cancer staging, $550.08 for axillary staging of breast cancer, $230.75-$2301.27 for assessment of recurrent colorectal cancer and $300.24-$2069.65 for assessment of myocardial viability. Significant differences in disease prevalence and PET specificity could occur while the cost-effectiveness of PET was preserved. Decision tree sensitivity analysis can demonstrate the cost-effectiveness of diagnostic imaging modalities in Australia and provides indications that PET is cost-effective for a range of clinical indications.