Currently definitive diagnosis of skin cancer requires assessment of biopsied tissue, which in turn necessitates an invasive procedure that results scarring and significant costs to the medical system. During skin cancer treatment, visual assessment is also relied upon to determine the extent of the tumor, and therefore the amount of tissue to be either excised or irradiated. It is clear that all stages in the management of skin cancer would be facilitated by techniques that could provide accurate diagnostic information without multiple expensive and disfiguring skin biopsies. Our first project goal is to develop video rate non-invasive high resolution microscopy modalities for practically acquiring skin images in vivo with quality approaching that of histology images from biopsied tissue samples. Our second goal is to combine high resolution in vivo skin imaging with targeting biochemical analysis of identified skin microstructures to create a most powerful non-invasive diagnostic tool for skin cancer detection and evaluation. Successful development of the proposed device will substantially improve the quality of life for patients with suspected and proven skin cancer by minimizing unnecessary diagnostic surgical biopsies and facilitating definitive skin cancer treatment at early curable stages.