Purpose: Of this study is to evaluate the role of greyscale ultrasound and duplex sonography in differentiating benign from malignant musculoskeletal soft tissue masses, in order to assess whether these methods are able to increase the diagnostic accuracy of grayscale ultrasonography. Materials and methods: all 50 Patients with palpable soft tissue masses of all age groups and both genders were included, excluding Inflammatory masses (like abscesses, cellulitis, and pyomyositis) and trauma. All patients were examined by means of available equipment Mindray DC–30 series ultrasound machine and confirmed by FNAC/histopathology of the masses. Depending on the size and depth of the lesion, curved array or linear probes were used 5–1 MHz and 15–6 MHz, respectively Results: grayscale ultrasonography showed 75% sensitivity, 63% specificity, 57% positive predictive value, 79% negative predictive value and 68% accuracy in differentiating benign from malignant lesions while combined evaluation ultrasound showed increase; 80% sensitivity, 93% specificity, 88% positive predictive value, 87% negative predictive value and 88% accuracy in differentiating malignant from benign lesions. Low Resistive indices (= or less than 0.5) of the internal vessels within the tumors also showed significant correlation with the malignant nature of the lesion Conclusion: duplex ultrasound assessment of MSK soft tissue masses might represent an important supplement to greyscale sonography and should always be performed when evaluating the same by ultrasonography.