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Breast cancer screening and longitudinal monitoring require imaging technologies that are portable, operator-independent, and suitable for frequent use, a capability not fully met by mammography or conventional ultrasound. We present a three-dimensional (3D) portable ultrasound system for real-time examination (3D PURE) that overcomes key limitations in volumetric breast imaging through advances in transducer design, acoustic materials, and adaptive beamforming. A box-array design incorporating a corner-gap offset geometry suppresses peak crosstalk (by 3.73 dB at the corner-most element), prevents preamplifier saturation, and supports higher transmit voltages (up to 24 V). A custom flowable backing layer (impedance 6.12 MRayl; attenuation 7.56 dB mm^-1 MHz^-1) integrates around fragile wirebonds, reduces inter-element crosstalk by ~4.5 dB throughout the array, and improves axial and lateral/elevational resolutions by ~200 µm and ~70 µm, respectively. Layered Aberration-Correction Reconstruction (LACR), an adaptive 3D beamformer, compensates for heterogeneous speed-of-sound (SoS) in the breast, reducing depth localization error by 2 mm and aberration defocusing by 70 µm on average at a 5 cm depth. Nine of the ten participants in an in vitro study showed improved microtarget detection efficiency with 3D PURE relative to a conventional 2D system (p = 0.0215), analogous to detection of microcalcifications. These results, combined with in vivo imaging validation of various phenotypes, highlight the potential of 3D PURE for reliable breast imaging. Furthermore, a vision-guided computer interface, MyFUS, ensures self-guided, user-friendly, and operator-independent probe positioning for longitudinal monitoring.