Wirtzfeld et al. report the first use of three-dimensional ultrasound microimaging for measuring tumor progression in a genetically engineered mouse model, the 94-amino acid prostate secretory protein (PSP94) gene-directed transgenic prostate cancer model. The upper panel shows orthogonal planes through a three-dimensional ultrasound image of a ventral prostate tumor in one of the genetically engineered mice. The maximum diameter of this tumor is 7.3 mm. The lower panel shows orthogonal planes through a three-dimensional reconstruction of H&E-stained serial histology slides of the same tumor. The histology reconstruction indicates that the tumor includes an outer region with a high density of sheets of poorly differentiated prostate cancer cells surrounding a central core containing vascular and hemorrhaged regions within a lower density of poorly differentiated cancer cells. These regions correspond to areas of lower and higher brightness, respectively, in the ultrasound image. This comparison demonstrates the ability of noninvasive ultrasound microimaging to accurately depict the size and shape of malignant masses in live mice and suggests some histologic features of the PSP94 prostate cancer model that may contribute to tumor identification in ultrasound microimages. For details, see the article by Wirtzfeld et al. on page 6337 of this issue.