Gamma rays have been extensively investigated for breast imaging using collimators; however, the coded-aperture technique needs to be investigated more. In this paper, we propose an experimental study and Geant4 simulations of MURA mask breast imaging. First, we compare the experimental data against the simulation results carried out using Geant4 (version 10.4) and accreditation phantom. Second, we virtually extend our work by changing the tumor-to-background (TBR) and lesion location parameters. We used 99mTc as a radioactive source. Good agreement has been seen for the benchmark stage, especially in terms of tumor localization. Moreover, the calculated full width at half maximum (FWHM) and contrast for decoded images (having average values of 8 and 3.5 for TBR between 2 and 10) permitted us to conclude that we can accurately localize small lesions up to lower TBR values by following the decoding procedure of deducing the image of a “blank phantom” (phantom with TBR = 1) every time within a matlab-based program. Hence, this work can be considered a continuously added value to previous investigations for scintimammography imaging.