A system and method of quantifying uptake of radionuclide by tumor with the use of an MBI system equipped with an ultrasound unit. The quantification is effectuated based on comparison a first photon count (determined from an MBI image of a region of interest encompassing both the tumor and background tissue of the sample) and a second photon count (determined from an MBI image of a region of a substantially co-extensive region of interest that encompasses only background tissue and is devoid of tumor), and based on the values of depth of tumor and its size determined from the ultrasound imaging data.