Cancers of the skin are the most common forms of cancer in men and women, and account for nearly half of all malignancies. In 2009, more than 1 million cases were expected in the United States. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), two types of nonmelanomatous lesions associated with aging and sun exposure, are responsible for more than 800,000 cases per year. Recent studies have also linked nonmelanoma skin cancer (NMSC) to prior cancer therapy, especially radiation therapy. While NMSC is rarely lethal, these lesions are associated with other malignancies (including hematologic and respiratory tract cancers). In contrast, melanoma accounts for approximately 4 percent of all skin cancer cases, but causes the majority of skin cancer deaths. One study found that melanoma incidence rates had doubled in all socioeconomic groups over a 10-year period. Another study found that melanoma incidence rates have increased by 3 percent per year in white Hispanic and white non-Hispanic populations, and both white Hispanic and Black populations had more advanced disease at presentation. Melanoma is associated with significant morbidity, and late stage melanoma with significant mortality due to the likelihood of metastatic spread. Therefore, timely diagnosis and treatment are critical to reducing rates of morbidity and mortality of all skin cancers. However, suboptimal diagnostic accuracy of current methods of lesion assessment (such as visual inspection) may lead to misleading false positives or conversely missed diagnoses, and the existing protocol of excisional biopsy of suspected lesions is an invasive, costly, and time-intensive procedure. Newer noninvasive screening and diagnostic modalities are available that may provide more precise imaging of suspected lesions and more accurate detection, thereby improving in vivo diagnosis. These newer technologies may, therefore, assist with earlier detection, eliminate unnecessary biopsies, and reduce costs and patient time spent in the physician's office. Several groups in Europe, North America, Australia, and New Zealand have developed guidelines for the screening and prevention of skin cancer. According to a 2009 Guideline Synthesis, while there is general agreement that there is insufficient evidence to support screening of the general population for skin cancer, increased surveillance for individuals at higher risk is generally recommended. The objectives of this technical brief are to provide a description of the state of the science of noninvasive imaging modalities in diagnosing cancerous tumors of the skin, proffer an analytic framework for assessing the applications of the devices, provide a summary of ongoing research, and to delineate future research needs. Three principal forms of skin cancer will be considered: basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), the more prevalent forms of skin cancer, and melanoma, among the most virulent. While the focus of this brief will be on modalities currently in general or limited clinical use and/or FDA approved or cleared, we also will consider investigational technologies based on available data and input from our key informants particularly the potential importance of these technologies and where they might fit into the care process.