OBJECTIVE Speed-of-sound (SoS) has large potential for tissue and pathology differentiation. We aim to develop a novel Ultrasound Computed Tomography (USCT) technique that can reconstruct local SoS in tissue on conventional ultrasound machines with hand-held linear arrays. METHODS A passive reflector is placed opposite the tissue sample as an echogenic reference to measure the time-of-flight (ToF) of ultrasound wave- fronts. A Dynamic Programming algorithm provides a robust ToF measurements based on global optimization of all transmit- receive echo data. An Anisotropically-Weighted Total Variation (AWTV) algorithm allows sharp delineation of focal lesions based on limited-angle USCT data. RESULTS Inclusions, which are not visible in conventional ultrasound, could be delineated in SoS images. AWTV allows to reconstruct focal lesions with a contrast-ratio of 93.7% of their nominal value, compared to that of 31.5% with conventional least-squares based algebraic tomographic reconstruction. In full-wave simulations of realistic heterogeneous breast models, a high CR of 84.3% is observed, with the reconstruction filtering out background heterogeneity. In experiments, our proposed method quantifies SoS in a homogeneous background with an accuracy of 0.93ms, allowing to differentiate several tissue types. CONCLUSION We validate our method using numerical simulations with ray-tracing and full- wave models, and phantom and ex-vivo data. Preliminary in- vivo results show the potential of this new technique to detect and differentiate malignant and benign lesions in the breast. SIGNIFICANCE Breast cancer is the most common cancer in women. Ultrasound B-mode only provides qualitative information about breast lesions, whereas USCT can provide quantitative tissue imaging biomarkers, such as SoS. The proposed method can potentially be implemented as a complementary modality to ultrasound for tissue and disease differentiation.