The goal of this study was to validate high-frequency (24 MHz) ultrasound imaging techniques for early detection and follow-up of renal tumors in a murine Wilms' tumor model (n = 26). For 11 mice, maximum tumor dimensions were estimated from images along three orthogonal axes for comparison with posteuthanasia caliper and histologic measurements. Tumor size in the 15 remaining mice was checked biweekly. The mice were then euthanized and histologic study assessed tumor position and nature. Tumors were detected in vivo between 7 to 14 days after injection of tumor-inducing cells. Tumor maximum cross-sectional area varied from 0.07 mm2 to 5.7 mm2 at the time of initial detection. The relative r.m.s. error between ultrasonic and histologic estimations of maximum cross-sectional area was estimated to be 19%. Results demonstrate feasibility of noninvasive ultrasound biomicroscopy early detection and characterization of renal tumor development for longitudinal monitoring of the same animal.