H-scan is a new ultrasound (US) technique that images the relative size of acoustic scatterers. This modality relies on matching a model of pulse-echo formation to the mathematics of a class of Gaussian-weighted Hermite polynomials (GH). Parallel convolution filters using the second (GH2) and eighth (GH8) components are applied to the radio frequency (RF) US data to capture the low and high frequency signal components, respectively. The relative strength from each convolution is color-coded and imaged. The purpose of this study was to evaluate the potential of H-scan imaging for characterizing tumor tissue and any early response to systemic anticancer treatment. Preliminary in vivo H-scan imaging studies were performed using an animal model of breast cancer. B-scan and H-scan imaging was performed before and after injection of an anticancer drug (albumin-bound paclitaxel) to assess any early tumor response and cellular disruption. Imaging was repeated along the same tumor cross-section every 30 min for at least 2 h. The results show that there was a significant overall change in the mean H-scan image intensity (compared to baseline measurements) at 120 min (29.2 ± 0.8%, p = 0.001). At this same time point, there was also a decrease in the B-scan image intensity (18.4 ± 3.0%, p = 0.03). Preliminary examples presented suggest that H-scan imaging is a promising tissue characterization modality. Further, H-scan may provide prognostic value during monitoring of the early tumor response (or lack thereof) to anticancer treatment.