Optical Coherence Tomography (OCT) is a recently developed imaging technology, which permits in-situ, real-time, non-invasive, non-contact, cross-sectional imaging of micron-scale structures in biological tissues and as such seems to be a suitable modality for the study of skin cancer. The development of polarization sensitive optical coherence tomography (PS-OCT) permits the acquisition additional information on the polarization properties of tissue carried by the reflected light. Malignant melanoma, a form of skin cancer, is increasing in incidence at the most rapid rate of all cancers. Yet detection of melanoma visually, even by experts in melanoma, has only 60-80% sensitivity. Thus, new methods of analyzing suspicious skin lesions in vivo are urgently needed. In this proposed study, we will construct a PS-OCT system to distinguish between normal, benign and malignant tissues. The PS-OCT system will control the polarization state of the light incident upon the sample. By measuring the reflectivity of light returning in particular polarization states we will obtain the Mueller matrix that provides complete representation of the polarization properties of the sample. During the first year of this project, we will complete construction and refinement of a high speed PS-OCT system by using a rapid scan optical delay line. In the second year, a transgenic mouse model will be used in conjunction with PS-OCT to study multistage melanoma carcinogenesis and differentiation of benign and 1 malignant lesions. This transgenic mouse model uses tyrosinase promoter to target expression of the mutated human T24 Ha-ras oncogene, as previously developed by Dr. Powell who will serve as a consultant in the second year. The overall goals of developing a system capable of determining benign from malignant pigmented lesions will be achieved through the following specific aims: (1) develop PS-OCT instrumentation, (2) compare PS-OCT and histology to differentiate benign from malignant lesions. Successful completion of this pilot project will further the development of a practical and inexpensive device that can be used to differentiate benign from malignant lesions of the skin. Thus this research will have the potential to improve patient care and reduce the human and economical cost of melanoma.