Non-Invasive Skin Cancer Diagnosis by Electrical Impedance Spectroscopy: Biophysics, Devices, Clinical Evidence, and Future Directions.

Skin cancer represents a growing global health burden. Current diagnostic pathways combine clinical examination and dermoscopy with histopathological confirmation; however, overlap between benign and malignant lesions can create diagnostic uncertainty and lead to potentially avoidable biopsies. Electrical impedance spectroscopy (EIS) has emerged as a non-invasive technique with potential for portable and cost-efficient implementation that quantifies the dielectric contrast between malignant and healthy tissue, providing objective information that may support clinical decision-making. This review synthesizes the field across four levels. First, we describe the biophysical origins of the impedance contrast in skin cancer, spanning the cellular, tissue architecture, and molecular scales, together with the equivalent circuit and Cole-Cole frameworks used to interpret it. Second, we examine hardware advances, including electrode-skin interface strategies, flexible and wearable architectures, computational electrode design, and the translation from laboratory prototypes to commercial systems such as Nevisense. Third, we critically appraise clinical evidence from large multicenter trials, focusing on the sensitivity-specificity trade-off and the demonstrated reduction in the number needed to excise. Finally, we discuss emerging frontiers, including artificial intelligence-driven analysis and multimodal fusion with dermoscopy, reflectance confocal microscopy, optical coherence tomography, and near-infrared spectroscopy. We conclude that EIS is most valuable as a complementary component within an integrated, AI-supported multimodal diagnostic framework.