jats:pUnsupervised segmentation techniques, which do not require labeled data for training and can be more easily integrated into the clinical routine, represent a valid solution especially from a clinical feasibility perspective. Indeed, large-scale annotated datasets are not always available, undermining their immediate implementation and use in the clinic. Breast cancer is the most common cause of cancer death in women worldwide. In this study, breast lesion delineation in Dynamic Contrast Enhanced MRI (DCE-MRI) series was addressed by means of four popular unsupervised segmentation approaches: Split-and-Merge combined with Region Growing (SMRG), k-means, Fuzzy C-Means (FCM), and spatial FCM (sFCM). They represent well-established pattern recognition techniques that are still widely used in clinical research. Starting from the basic versions of these segmentation approaches, during our analysis, we identified the shortcomings of each of them, proposing improved versions, as well as developing ad hoc pre- and post-processing steps. The obtained experimental results, in terms of area-based—namely, Dice Index (DI), Jaccard Index (JI), Sensitivity, Specificity, False Positive Ratio (FPR), False Negative Ratio (FNR)—and distance-based metrics—Mean Absolute Distance (MAD), Maximum Distance (MaxD), Hausdorff Distance (HD)—encourage the use of unsupervised machine learning techniques in medical image segmentation. In particular, fuzzy clustering approaches (namely, FCM and sFCM) achieved the best performance. In fact, for area-based metrics, they obtained DI = 78.23% ± 6.50 (sFCM), JI = 65.90% ± 8.14 (sFCM), sensitivity = 77.84% ± 8.72 (FCM), specificity = 87.10% ± 8.24 (sFCM), FPR = 0.14 ± 0.12 (sFCM), and FNR = 0.22 ± 0.09 (sFCM). Concerning distance-based metrics, they obtained MAD = 1.37 ± 0.90 (sFCM), MaxD = 4.04 ± 2.87 (sFCM), and HD = 2.21 ± 0.43 (FCM). These experimental findings suggest that further research would be useful for advanced fuzzy logic techniques specifically tailored to medical image segmentation.</jats:p>