As a result of increasing melanoma incidence and challenges with clinical and histopathologic evaluation of pigmented lesions, noninvasive techniques to assist in the assessment of skin lesions are highly sought after. This review discusses the methods, benefits, and limitations of adhesive patch biopsy, electrical impedance spectroscopy (EIS), multispectral imaging, high-frequency ultrasonography (HFUS), optical coherence tomography (OCT), and reflectance confocal microscopy (RCM) in the detection of skin cancer. Adhesive patch biopsy provides improved sensitivity and specificity for the detection of melanoma without a trade-off of higher sensitivity for lower specificity seen in other diagnostic tools to aid in skin cancer detection, including EIS and multispectral imaging. EIS and multispectral imaging provide objective information based on computer-assisted diagnosis to assist in the decision to biopsy and/or excise an atypical melanocytic lesion. HFUS may be useful for the determination of skin tumor depth and identification of surgical borders, although further studies are necessary to determine its accuracy in the detection of skin cancer. OCT and RCM provide enhanced resolution of skin tissue and have been applied for improved accuracy in skin cancer diagnosis, as well as monitoring the response of nonsurgical treatments of skin cancers and the determination of tumor margins and recurrences. These novel approaches to skin cancer assessment offer opportunities to dermatologists, but are dependent on the individual dermatologist’s comfort, knowledge, and desire to invest in training and implementation of noninvasive techniques. These noninvasive modalities may have a role in the complementary assessment of skin cancers, although histopathologic diagnosis remains the gold standard for the evaluation of skin cancer.

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