Ultrasound-guided diffuse optical tomography (DOT) is a promising imaging technique that maps hemoglobin concentrations of breast lesions to assist ultrasound (US) for cancer diagnosis and treatment monitoring. The accurate recovery of breast lesion optical properties requires an effective image reconstruction method. We introduce a reconstruction approach in which US images are encoded as prior information for regularization of the inversion matrix. The framework of this approach is based on image reconstruction package “NIRFAST.” We compare this approach to the US-guided dual-zone mesh reconstruction method, which is based on Born approximation and conjugate gradient optimization developed in our laboratory. Results were evaluated using phantoms and clinical data. This method improves classification of malignant and benign lesions by increasing malignant to benign lesion absorption contrast. The results also show improvements in reconstructed lesion shapes and the spatial distribution of absorption maps.