Optical imaging using independent component analysis (OPTICA) has been used for detection, 3D localization, and cross-section imaging of a tumor inside a model human breast composed of ex vivo human breast tissues. OPTICA uses a multisource target illumination and multidetector signal acquisition scheme to obtain multiple spatial and angular views of the sample for target localization. Independent component analysis of the perturbations in the spatial light intensity distribution measured on the sample boundary sorts out the signal originating from individual targets. A back-projection technique estimates the cross-section of each target. The approach correctly provided the positions of a tumor located at the mid-plane and two glandular structures located at different positions within the 33-mm thick model breast. The reconstructed cross-section images are in good agreement with known dimensions of the structures, and pathological findings.