Mammography is the only technique currently used for detecting microcalcification (MC) clusters, an early indicator of breast cancer. However, mammographic images superimpose a three-dimensional compressed breast image onto two-dimensional projection views, resulting in overlapped anatomical breast structures that may obscure the detection and visualization of MCs. One possible solution to this problem is the use of cone beam computed tomography (CBCT) with a flat-panel (FP) digital detector. Although feasibility studies of CBCT techniques for breast imaging have yielded promising results, they have not shown how radiation dose and x-ray tube voltage affect the accuracy with which MCs are detected by CBCT experimentally. We therefore conducted a phantom study using a FP-based CBCT system with various mean glandular doses and kVp values. An experimental CBCT scanner was constructed with a data acquisition rate of 7.5 frames/s. 10.5 and 14.5 cm diameter breast phantoms made of gelatin were used to simulate uncompressed breasts consisting of 100% glandular tissue. Eight different MC sizes of calcium carbonate grains, ranging from 180-200 microm to 355-425 microm, were used to simulate MCs. MCs of the same size were arranged to form a 5 x 5 MC cluster and embedded in the breast phantoms. These MC clusters were positioned at 2.8 cm away from the center of the breast phantoms. The phantoms were imaged at 60, 80, and 100 kVp. With a single scan (360 degrees), 300 projection images were acquired with 0.5 x, 1x, and 2x mean glandular dose limit for 10.5 cm phantom and with 1x, 2x, and 4x for 14.5 cm phantom. A Feldkamp algorithm with a pure ramp filter was used for image reconstruction. The normalized noise level was calculated for each x-ray tube voltage and dose level. The image quality of the CBCT images was evaluated by counting the number of visible MCs for each MC cluster for various conditions. The average percentage of the visible MCs was computed and plotted as a function of the MGD, the kVp, and the average MC size. The results showed that the MC visibility increased with the MGD significantly but decreased with the breast size. The results also showed that the x-ray tube voltage affects the detection of MCs under different circumstances. With a 50% threshold, the minimum detectable MC sizes for the 10.5 cm phantom were 348(+/-2), 288(+/-7), 257(+/-2) microm at 3, 6, and 12 mGy, respectively. Those for the 14.5 cm phantom were 355 (+/-1), 307 (+/-7), 275 (+/-5) microm at 6, 12, and 24 mGy, respectively. With a 75% threshold, the minimum detectable MC sizes for the 10.5 cm phantom were 367 (+/-1), 316 (+/-7), 265 (+/-3) microm at 3, 6, and 12 mGy, respectively. Those for the 14.5 cm phantom were 377 (+/-3), 334 (+/-5), 300 (+/-2) microm at 6, 12, and 24 mGy, respectively.