Understanding the effect of overlaying tissues on HIFU lesion is crucial for estimating HIFU dose distribution at a target tissue. We have run a series of experiments to systematically observe the effects of the overlaying tissues on the HIFU beam and ultimately the lesion created in the target tissue. First, we mapped out the HIFU transducer beam (in low power) under water without and with different overlaying tissue layers. Then, we performed a series of experiments in high power to create lesions in target tissues (e.g., liver) without and with overlaying tissues (e.g. muscle). The lesions are characterized by slicing the tissues and reconstructing the 3D lesion from calibrated pictures of the target tissue slices. The low power beam measurements show significant effects in terms of severe beam wave‐field amplitude distortion due to phase aberration introduced by velocity inhomogeneity in the overlaying tissues. These results compare well qualitatively with the computational models. The results from the high power HIFU lesions in a similar setup using various tissues, including liver and muscle, provide understanding of the significance of phase aberration in overlaying tissues and could prove useful towards high precision HIFU therapy.