Fusion-based ultrasound (US)-guided biopsy in a breast is challenging due to the high deformability of the tissue combined with the fact that the breast is usually differently deformed in CT, MR, and US acquisition which makes registration difficult. With this phantom study, we demonstrate the feasibility of a fusion-based ultrasound-guided method for breast biopsy. 3D US and 3D CT data were acquired using dedicated imaging setups of a breast phantom freely hanging in prone position with lesions. The 3D breast CT set up was provided by Koning (Koning Corp., West Henrietta, NY). For US imaging, a dedicated breast scanning set up was developed consisting of a cone-shaped revolving water tank with a 152- mm-sized US transducer mounted in its wall and an aperture for needle insertion. With this setup, volumetric breast US data (0.5×0.5×0.5 mm3 voxel size) can be collected and reconstructed within 3 minutes. The position of the lesion as detected with breast CT was localized in the US data by rigid registration. After lesion localization, the tank rotates the transducer until the lesion is in the US plane. Since the lesion was visible on ultrasound, the performance of the registration was validated. To facilitate guided biopsy, the lesion motion, induced by needle insertion, is estimated using cross-correlation-based speckle tracking and the tracked lesion visualized in the US image at an update frequency of 10 Hz. Thus, in conclusion a fusion-based ultrasound-guided method was introduced which enables ultrasound-guided biopsy in breast that is applicable also for ultrasound occult lesions.