The purpose of this study was to explore the treatment planning methods of spatially fractionated radiation therapy (SFRT), commonly referred to as GRID therapy, in the treatment of breast cancer patients using multileaf collimator (MLC) in the prone position. A total of 12 patients with either left or right breast cancer were retrospectively chosen. The computed tomography (CT) images taken for the whole breast external beam radiation therapy (WB‐EBRT) were used for GRID therapy planning. Each GRID plan was made by using two portals and each portal had two fields with 1‐cm aperture size. The dose prescription point was placed at the center of the target volume, and a dose of 20 Gy with 6‐MV beams was prescribed. Dose‐volume histogram (DVH) curves were generated to evaluate dosimetric properties. A modified linear‐quadratic (MLQ) radiobiological response model was used to assess the equivalent uniform doses (EUD) and therapeutic ratios (TRs) of all GRID plans. The DVH curves indicated that these MLC‐based GRID therapy plans can deliver heterogeneous dose distribution in the target volume as seen with the conventional cerrobend GRID block. The plans generated by the MLC technique also demonstrated the advantage for accommodating different target shapes, sparing normal structures, and reporting dose metrics to the targets and the organs at risks. All GRID plans showed to have similar dosimetric parameters, implying the plans can be made in a consistent quality regardless of the shape of the target and the size of volume. The mean dose of lung and heart were respectively below 0.6 and 0.7 Gy. When the size of aperture is increased from 1 to 2 cm, the EUD and TR became smaller, but the peak/valley dose ratio (PVDR) became greater. The dosimetric approach of this study was proven to be simple, practical and easy to be implemented in clinic.