Fifty-six patients with soft tissue masses of the limbs (36 benign, 20 malignant) prospectively underwent sonography (color Doppler and pulsed Doppler examinations) to assess the role of Doppler interrogation in differentiating benign from malignant lesions. Sonography showed 60% sensitivity, 55% specificity, 71% negative predictive value, 42% positive predictive value, and 57% accuracy. Color Doppler evaluation showed 85% sensitivity, 88% specificity, 91% negative predictive value, 80% positive predictive value, and 87% accuracy. Diastolic and venous velocities and pulsatility index values were not statistically significant. Mean systolic velocity was 0.27 m/s in benign lesions and 0.55 m/s in malignant lesions. By combining sonographic and Doppler data, a correct diagnosis was obtained in 51 of 56 patients (90% sensitivity, 91% specificity, 85% positive predictive value, 94% negative predictive value, 91% accuracy). Color Doppler and pulsed Doppler evaluations represent a useful adjunct to sonography and should be routinely included in the evaluation of musculoskeletal soft tissue masses by ultrasonography.