Our objective was to assess the role of quantitative Doppler vascularity in differentiating malignant and benign thyroid nodules. Color Doppler images of 100 nodules were analyzed for three metrics: vascular fraction area, mean flow velocity index and flow volume index in three regions (nodule center, nodule rim and surrounding parenchyma). Vascular fraction area and flow volume index were higher in malignant than benign nodules in both the central and rim regions, whereas flow velocity index was equivalent in both regions. Of the three vascularity metrics studied, the vascular fraction area of the central region was most effective in predicting malignancy, with a sensitivity of 0.90 ± 0.05, specificity of 0.88 ± 0.13, positive predictive value of 0.84 ± 0.14, negative predictive value of 0.92 ± 0.03 and accuracy of 0.89 ± 0.08. Quantitative Doppler vascularity of the nodule center yielded a high level of discrimination between benign and malignant nodules and, thus, has the greatest potential to contribute to gray-scale assessment of thyroid cancer.