Recent advances in optical imaging have led to the introduction of new techniques that promise to become a powerful guidance tool in tumor excision surgery. A technique suitable for the intraoperative delineation of cancer margins should combine real-time imaging capability with sufficient accuracy. Development of several optical techniques including multi-spectral dye-enhanced reflectance macro-imaging, confocal microscopy, exogenous fluorescence, and reflectance polarization imaging will be discussed in the context of nonmelanoma skin cancer demarcation. Results yielded by each method will be presented and compared to each other and histopathology. Possibility of combining two or more of these imaging techniques in a single modality for increasing the sensitivity and specificity of the resulting method will be considered and analyzed.