The purpose of this study is to determine if microvascular tortuosity can be used as an imaging biomarker for the presence of tumor-associated angiogenesis and if imaging this biomarker can be used as a specific and sensitive method of locating solid tumors. Acoustic angiography, an ultrasound-based microvascular imaging technology, was used to visualize angiogenesis development of a spontaneous mouse model of breast cancer (n = 48). A reader study was used to assess visual discrimination between image types, and quantitative methods utilized metrics of tortuosity and spatial clustering for tumor detection. The reader study resulted in an area under the curve of 0.8, while the clustering approach resulted in the best classification with an area under the curve of 0.95. Both the qualitative and quantitative methods produced a correlation between sensitivity and tumor diameter. Imaging of vascular geometry with acoustic angiography provides a robust method for discriminating between tumor and healthy tissue in a mouse model of breast cancer. Multiple methods of analysis have been presented for a wide range of tumor sizes. Application of these techniques to clinical imaging could improve breast cancer diagnosis, as well as improve specificity in assessing cancer in other tissues. The clustering approach may be beneficial for other types of morphological analysis beyond vascular ultrasound images.