In this study, we demonstrated the contrast-to-noise ratio (CNR) improvement in breast cone beam CT (CBCT) using the volume-of-interest (VOI) scanning technique. In VOI breast CBCT, the breast is first scanned at a low exposure level. A pre-selected VOI is then scanned at a higher exposure level with collimated x-rays. The two image sets are combined together to reconstruct high quality 3-D images of the VOI. A flat panel detector based system was built to demonstrate and investigate the CNR improvement in VOI breast CBCT. The CNRs of the 8 plastic cones (Teflon, Delrin, polycarbonate, Lucite, solid water, high density polystyrene, nylon and polystyrene) in a breast phantom were measured in images obtained with the VOI CBCT technique and compared to those measured in standard full field CBCT images. CNRs in VOI CBCT images were found to be higher than those in regular CBCT images in all plastic cones. The mean glandular doses (MGDs) from the combination of a high exposure VOI scan and a low exposure full-field scan was estimated to be similar to that from regular full-field scan at standard exposure level. The VOI CBCT technique allows a VOI to be imaged with enhanced image quality with an MGD similar to that from regular CBCT technique.