Ultrasound is a leading image-guidance modality for noninvasive surgery using high intensity focused ultrasound (HIFU). Its low cost and portability, together with its high frame rates, are among its well-known advantages. However, ultrasound's poor soft-tissue contrast continues to limit the specificity of image feedback on local tissue changes due to the application of HIFU beams. This limitation is being addressed by developing nonlinear pulse-echo imaging methods for monitoring of lesion formation with HIFU. In this paper, we provide the first in vivo results from an investigation of two nonlinear methods for this purpose. Specifically, pulse inversion (PI) and quadratic B-mode (QB-mode) are compared with standard B-mode imaging. An integrated system employing a HIFU transducer and a diagnostic scanner was used. Beam-formed RF data was acquired in real-time before, during, and after HIFU-lesion formation and processed off-line to produce B-mode, PI-mode, and QB-mode images for comparison. The imaging target was a LNCaP Pro 5 human prostate tumor implanted in the hind limb of nude mice and carefully positioned at the intersection of the imaging plane and the HIFU focus. The results show clearly that both QB-mode and PI-mode improve the lesion contrast compared to standard B-mode (6 dB or more for typical lesions). The results also show that QB-mode offers the advantage of improved dynamic range when compared to PI-mode imaging (by 30 dB or higher). These in vivo results show that QB-mode imaging offers a guidance modality with high sensitivity and specificity to tissue changes at the therapeutic HIFU focus without loss in spatial resolution.