Gold nanorods (GNRs) combined with two-photon microscopy were explored for potential application in imaging of oral carcinogenesis. GNRs have been shown to be effective contrast agents for two photon luminescence in that excitation laser powers required for imaging are low compared to traditional fluorophores. Imaging of cells, ex vivo tissues, and in vivo oral mucosa labeled with GNRs was performed to evaluate potential advantages of these agents in molecular imaging of epithelial carcinogenesis. Powers required to elicit a two-photon luminescence signal from GNRs were determined for cells as well as normal and malignant transformed lesions, 24 hours following injection of GNRs in a hamster model for oral cancer. The strength of the detected emission as the function of the average incident laser power was measured in tissues with and without GNRs to compare the sensitivity of GNRs against tissue autofluorescence. Finally, in vivo imaging was performed immediately following GNR injection to establish the ability to image microvasculature at low incident powers. The pilot study demonstrated uptake of GNRs by cells and in tissues yielding bright fluorescence signals using significantly lower incident powers than those needed to excite tissue autofluorescence. The in vivo imaging aspect of the study demonstrated the localization of GNRs within the microvasculature of the oral cancer model. These preliminary studies demonstrated the ability of GNRs to function as photostable, high contrast imaging agents and suggest that GNRs and multi-photon imaging have great potential for applications in the field of molecular imaging and early detection of cancer.