High resolution ultrasound (HR-US) including color Doppler ultrasound (CD-US), power Doppler ultrasound (PD-US), and spectral wave analysis (SWA), is a broadly available, non-invasive and relatively low-cost modality without ionizing radiation. It is increasingly used for initial assessment of an ambiguous musculoskeletal soft-tissue lesion and for sonographically guided core biopsy. The aim of this review is to provide sonographic findings of the most frequent benign and malign soft-tissue lesions. By this essay, we can show that combined with clinical features, with information on tumor-localization and patient age, many musculoskeletal lesions may be successfully characterized by HR-US. In contrast, a mere morphologic assignment of some fibrous tumors and malignant lesions remains often impossible; however, certain CD-US signs such as anarchic vascular architecture or arteriovenous shunting may be very helpful indicators for malignancy. HR-US offers a simple, quick, and reliable first-line examination of musculoskeletal soft-tissue lesions and may have an important role in the diagnostic work-up followed by magnetic resonance or multimodality imaging and guided core biopsy.