Breast tumor volume measured on MRI has been used to assess response to neoadjuvant chemotherapy. However, accurate and reproducible delineation of breast lesions can be challenging, since the lesions may have complicated topological structures and heterogeneous intensity distributions. In this article, the authors present an advanced computerized method to semiautomatically segment tumor volumes on T1-weighted, contrast-enhanced breast MRI. The method starts with manual selection of a region of interest (ROI) that contains the lesion to be segmented in a single image, followed by automated separation of the lesion volume from its surrounding breast parenchyma by using a unique combination of the image processing techniques including Gaussian mixture modeling and a marker-controlled watershed transform. Explicitly, the Gaussian mixture modeling is applied to an intensity histogram of the pixels inside the ROI to distinguish the tumor class from other tissues. Based on the ROI and the intensity distribution of the tumor, internal and external markers are determined and the tumor contour is delineated using the marker-controlled watershed transform. To obtain the tumor volume, the segmented tumor in one slice is propagated to the adjacent slice to form an ROI in that slice. The marker-controlled watershed segmentation is then used again to obtain a tumor contour in the propagated slice. This procedure is terminated when there is no lesion in an adjacent slice. To reduce measurement variations possibly caused by the manual selection of the ROI, the segmentation result is refined based on an automatically determined ROI based on the segmented volume. The algorithm was applied to 13 patients with breast cancer, prospectively accrued prior to beginning neoadjuvant chemotherapy. Each patient had two MRI scans, a baseline MRI examination prior to commencing neoadjuvant chemotherapy and a 1 week follow-up after receiving the first dose of neoadjuvant chemotherapy. Blinded to the computer segmentation results, two experienced radiologists manually delineated all tumors independently. The computer results were then compared with the manually generated results using the volume overlap ratio, defined as the intersection of the computer- and radiologist-generated tumor volumes divided by the union of the two. The algorithm reached overall overlap ratios of 62.6% +/- 9.1% and 61.0% +/- 11.3% in comparison to the two manual segmentation results, respectively. The overall overlap ratio between the two radiologists' manual segmentations was 64.3% +/- 10.4%. Preliminary results suggest that the proposed algorithm is a promising method for assisting in tumor volume measurement in contrast-enhanced breast MRI.