Distinguishing a tumor from non-neoplastic tissue is a challenging task during cancer surgery. Several attempts have been made to use visible or fluorescent agents to aid in the visualization of a tumor during surgery. We describe a novel method to delineate brain tumors, using a highly sensitive photoacoustic imaging technique that is enhanced by tumor-targeting blue nanoparticles serving as a contrast agent. Experiments on phantoms and on rat brains, , demonstrate the high sensitivity of photoacoustic imaging in delineating tumors containing contrast agent at a concentration much lower than needed for visualization by the naked eye. The limit of detection of the system for the nanoparticles is about 0.77 μg/mL in water (equivalent to 0.84 μmol/L Coomassie Blue dye). The present exploratory study suggests that photoacoustic imaging, when used with strongly optical absorbing contrast agents, could facilitate cancer surgery intraoperatively by revealing the distribution and extent of the tumor.