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In this paper, we study the transient thermal response of skin layers to determine to which extent the surface temperature distribution reflects the properties of subsurface structures, such as benign or malignant lesions. Specifically, we conduct a detailed sensitivity analysis to interpret the changes in the surface temperature distribution as a function of variations in thermophysical properties, blood perfusion rate, metabolic heat generation and thicknesses of skin layers, using a multilayer computational model. These properties can vary from individual to individual or depend on location, external and internal influences, and in certain situations accurate property data are not available in the literature. Therefore, the uncertainties in these data could potentially affect the accuracy of the interpretation/diagnosis of a lesion in a clinical setting. In this study, relevant parameters were varied within characteristic physiological …