A method has been devised for generating three-dimensional optical images of the breast using a 32-channel time-resolved system and a liquid-coupled interface. The breast is placed in a hemispherical cup surrounded by sources and detectors, and the remaining space is filled with a fluid with tissue-like optical properties. This approach has three significant benefits. First, cups can accommodate a large range of breast sizes, enabling the entire volume of the breast to be sampled. Second, the coupling of the source and detector optics at the surface is constant and independent of the subject, enabling intensity measurements to be employed in the image reconstruction. Third, the external geometry of the reconstructed volume is known exactly. Images of isolated targets with contrasting absorbing and scattering properties have been acquired, and the performance of the system has been evaluated in terms of the contrast, spatial resolution, and localization accuracy. These parameters were strongly dependent on the location of the targets within the imaged volume. Preliminary images of a healthy human subject are also presented, which reveal subtle heterogeneity, particularly in the distribution of scatter. The ability to detect an absorbing target adjacent to the breast is also demonstrated.