ObjectivesOne of the most promising adjuncts for screening breast cancer is ultrasound (US) radio‐frequency (RF) time series. It has the superiority of not requiring any supplementary equipment over other methods. This research aimed to propound a machine learning (ML) approach for automatically classifying benign, probably benign, suspicious, and malignant breast lesions based on the features extracted from the accumulated US RF time series.MethodsIn this article, 220 data of the aforementioned categories, recorded from 118 patients, were analyzed. The dataset, named RFTSBU, was registered by a SuperSonic Imagine Aixplorer medical/research system equipped with a linear transducer. The regions of interest (ROIs) of the B‐mode images were manually selected by an expert radiologist before computing the suggested features. Regarding time, frequency, and time‐frequency domains, 291 various features were extracted from each ROI. Finally, the features were classified by a pioneering technique named the reference classification method (RCM). Furthermore, the Lee filter was applied to evaluate the effectiveness of reducing speckle noise on the outcomes.ResultsThe accuracy of two‐class, three‐class, and four‐class classifications were respectively calculated 98.59 ± 0.71%, 98.13 ± 0.69%, and 96.10 ± 0.66% (considering 10 repetitions) while support vector machine (SVM) and K‐nearest neighbor (KNN) classifiers with 5‐fold cross‐validation were utilized.ConclusionsThis article represented the proposed approach, named CCRFML, to distinguish between breast lesions based on registered in vivo RF time series employing an ML framework. The proposed method's impressive level of classification accuracy attests to its capability of effectively assisting medical professionals in the noninvasive differentiation of breast lesions.