Although thyroid cancer has relatively good prognosis, the management of this disease is complicated by the large incidence of thyroid nodules in the adult population. Unfortunately, current imaging methods do not provide a sufficient level of accuracy in order to replace biopsy as a tool for diagnosis of thyroid cancer. A relatively recent study suggests that spectral-based quantitative ultrasonic methods may provide a new source of contrast when imaging thyroid nodules. In this study, two parameters (i.e., the effective scatterer diameter (ESD) and the effective acoustic concentration (EAC)) were estimated from a rodent model of follicular variant papillary thyroid carcinoma (FV-PTC) ex vivo. The mean ESD values were 21.5 ± 1.8 μm and 15.9 ± 0.8 μm for normal and diseased thyroids, respectively. Also, the mean EAC values were 52.9 ± 3.4 dB/cm and 62.7 ± 1.6 dB/cm for normal and diseased thyroids, respectively. A non-parametric Kruskal-Wallis test revealed statistically significant differences between FV-PTC and normal thyroids using both parameters (p < 0.05). Therefore, these preliminary results suggest that spectral-based quantitative ultrasound imaging may be useful for the management of thyroid cancer.