Noninvasive methods are strongly needed to detect and quantify not only tumor growth in murine tumor models but also the development of vascularization and necrosis within tumors. This study investigates the use of a new imaging technique, flat-panel detector volume computed tomography (fpVCT), to monitor in vivo tumor progression and structural changes within tumors of two murine carcinoma models. After tumor cell inoculation, single fpVCT scans of the entire mice were performed at different time points. The acquired isotropic, high-resolution volume data sets enable an accurate real-time assessment and precise measurements of tumor volumes. Spreading of contrast agent-containing blood vessels around and within the tumors was clearly visible over time. Furthermore, fpVCT permits the identification of differences in the uptake of contrast media within tumors, thus delineating necrosis, tumor tissues, and blood vessels. Classification of tumor tissues based on the decomposition of the underlying mixture distribution of tissue-related Hounsfield units allowed the quantitative acquisition of necrotic tissues at each time point. Morphologic alterations of the tumor depicted by fpVCT were confirmed by histopathologic examination. Concluding, our data show that fpVCT may be highly suitable for the noninvasive evaluation of tumor responses to anticancer therapies during the course of the disease.