Effective analysis of breast thermography needs an accurate segmentation of the inflamed region in Infrared Breast Thermal Images (IBTI) which helps in the diagnosis of breast cancer. However, IBTI suffers from intensity inhomogeneity, overlapping regions of interest, poor contrast, and low signal-to-noise ratio (SNR) due to the imperfect image acquisition process. To mitigate this, this work proposes an enhanced segmentation of the inflamed Region of Interest (ROI) using an active contour method driven by the multiscale local and global fitted image (MLGFI) model. The first phase proposes a bilateral histogram difference-based thresholding (BHDT) method for locating the inflamed ROI. This is then used for automatic initialization of active contours driven by MLGFI to segment the inflamed ROI from IBTI effectively. To prove the effectiveness of this segmentation method, its performance is compared with ground truth image and its accuracy is also evaluated with the state-of-the-art methods (Fuzzy C Means (FCM), Chan-Vese (CV-ACM), and K-means). From the analysis, it is found that the proposed method not only increases the precision and the segmentation accuracy but also reduces the oversegmentation and undersegmentation rate significantly. In the second phase, area-based feature (AF) and average intensity-based feature (AIF) along with the GLCM (gray level cooccurrence matrix) based second-order statistical features are extracted from the inflamed ROI. Based on these features, a system is developed to effectively classify the benign and malignant breast conditions. From the results, it is observed that the proposed model exhibits an improved accuracy of 91.5%, sensitivity of 91%, and specificity of 92% compared to the whole breast thermogram. Hence, it is concluded that the proposed method will improve the efficacy of thermal imaging in the diagnosis of breast cancer. © 2021 Nirmala Venkatachalam et al.