Disclosed are embodiments of methods of and systems for detecting and biopsying lesions with a cone beam computed tomography (CBCT) system. The system comprises, in some embodiments, a CBCT device configured to output a cone beam CT image of at least a portion of a patient's breast and a multi-axis transport module, having at least three degrees of freedom and configured to position a biopsy needle within a 3D frame of reference based on inputs received from the cone beam CT device. The transport module can be configured to place the biopsy needle adjacent to, or within, a target of interest within the breast. Also disclosed are embodiments of methods of and systems for testing CBCT systems with phantoms.