Traditionally, image studies evaluating the effectiveness of computer-aided diagnosis (CAD) use a single label from a medical expert compared with a single label produced by CAD. The purpose of this research is to present a CAD system based on Belief Decision Tree classification algorithm, capable of learning from probabilistic input (based on intra-reader variability) and providing probabilistic output. We compared our approach against a traditional decision tree approach with respect to a traditional performance metric (accuracy) and a probabilistic one (area under the distance-threshold curve-AuC dt ). The probabilistic classification technique showed notable performance improvement in comparison with the traditional one with respect to both evaluation metrics. Specifically, when applying crossvalidation technique on the training subset of instances, boosts of 28.26% and 30.28% were noted for the probabilistic approach with respect to accuracy and AuC dt , respectively. Furthermore, on the validation subset of instances, boosts of 20.64% and 23.21% were noted again for the probabilistic approach with respect to the same two metrics. In addition, we compared our CAD system results with diagnostic data available for a small subset of the Lung Image Database Consortium database. We discovered that when our CAD system errs, it generally does so with low confidence. Predictions produced by the system also agree with diagnoses of truly benign nodules more often than radiologists, offering the possibility of reducing the false positives.