Functionalized gold nanospheres undergo receptor mediated aggregation on cancer cells that overexpress the epidermal growth factor receptor (EGFR). This phenomenon leads to a red shift in the plasmon resonance frequency of the EGFR-targeted gold nanoparticles. Previously we demonstrated that highly selective detection of cancer cells can be achieved using the combination of multi-wavelength photoacoustic imaging and molecular specific gold nanoparticles. In this study, we use tissue models to evaluate the sensitivity of molecular specific photoacoustic imaging in detecting cancer cells labeled with EGFR-targeted gold nanoparticles. The results of our study indicate that highly sensitive detection of cancer cells is feasible using photoacoustic imaging and plasmonic gold nanoparticles.