Design and experimental verification of a phased array (PA) of 434 MHz water-loaded cavity-backed patch antennas is presented for hyperthermia treatment (HT) of locally advanced breast cancer (LABC). A staggered annular array of 18 antennas distributed across three rings with six antennas per ring and 40 mm ring spacing is presented for HT. The applicator performance is assessed on three-layered breast models of varying volumes (133-1286 cm3) with 64 cm3 tumor target at three different locations in the individual breast model, and an anatomically realistic patient model with LABC (46 cm3) in the upper outer quadrant. HT indicators for the optimized applicator indicated average power absorption ratio (aPAratio) ≥ 3.93 and 10.48, and hotspot to target quotient (HTQ) ≤ 1.34 and 1.08 in the large and small breast models, respectively. aPAratio and HTQ were 6.14 and 1.23 in the anatomically realistic model, respectively. Simulation results were experimentally verified on a 3-D phantom fabricated based on the patient model with thermo-dielectric properties of breast tissues. Temperature rise of 6.04 °C, 6.55 °C, and 5.5 °C measured for centered and two off-centered tumor locations in the phantom for 20 min heating, respectively, were in excellent agreement with the simulations without any significant healthy tissue hotspots. © 1963-2012 IEEE.