Optimizing the number and utility of features to use in a classification analysis has been the subject of many research studies. Most current models use end-classifications as part of the feature reduction process, leading to circularity in the methodology. The approach demonstrated in the present research uses item response theory (IRT) to select features independent of the end-classification results without the biased accuracies that this circularity engenders. Dichotomous and polytomous IRT models were used to analyze 30 histological breast cancer features from 569 patients using the Wisconsin Diagnostic Breast Cancer data set. Based on their characteristics, three features were selected for use in a machine learning classifier. For comparison purposes, two machine learning–based feature selection protocols were run—recursive feature elimination (RFE) and ridge regression—and the three features selected from these analyses were also used in the subsequent learning classifier. Classification results demonstrated that all three selection processes performed comparably. The non-biased nature of the IRT protocol and information provided about the specific characteristics of the features as to why they are of use in classification help to shed light on understanding which attributes of features make them suitable for use in a machine learning context. Graphical abstract