Systematic efforts are under way to develop fluorochromes and imaging systems for in-viva examinations of pathogenesis and of treatment at the molecular level. The rationale for such technologies is a) to elucidate molecular mechanisms of disease in unperturbed environments overtime, b) to allow earlier detection of disease based on molecular targets and c) to permit design of patient-specific treatments and monitor therapies on their molecular effect. Recently developed tomographic approaches promise to bring three-dimensional imaging capacity and quantification capability, significantly improving current in-vivo fluorescence detection methods mainly based in planar illumination techniques. fluorescent imaging systems can enable a highly versatile and cost-effective imaging practice and enable the transfer of several elegant in-vitro fluorescent assays to in-vivo application. Similarly to nuclear methods, optical tomography would greatly benefit from the combination of an imaging modality that yields anatomical contrast. From the different important imaging modalities available ultrasound may be a very advantageous alternative. First it interfaces well with optical imaging in that they can be both made extremely portable, small in dimensions and cost-efficient. Second they both use non-ionizing radiation so their combination yields similar operational simplicity. Ultimately a combined ultrasound-optical modality could yield a versatile and economic imaging system that in return can improve the overall current clinical applicability of ultrasound imaging and give simple but high-information imaging solutions to cancer imaging. Pre-clinical evaluation with small animals is proposed herein using high-resolution ultrasound and fluorescence molecular tomography. The hybrid system could offer anatomical information, functional information through ultrasound Doppler imaging and oxy- and deoxy- hemoglobin imaging by the optical system and finally molecular contrast via the use of target specific fluorochromes.