Calluses are thickened skin areas that develop due to repeated friction, pressure, or other types of irritation. While calluses are usually harmless and formed as a protective surface, they can lead to skin ulceration or infection if left untreated. As calluses are often not clearly visible to the patients, and some areas of dead skin can be missed during debridement, accessory tools can be useful in assessment and follow-up. The practical question addressed in this article is whether or not thermal imaging adds value to callus assessment. We have performed a theoretical analysis of the feasibility of thermographic imaging for callus identification. Our analytical calculations show that the temperature drop in the epidermis should be on the order of 0.1 °C for the normal epidermis in hairy skin, 0.9 °C for glabrous skin, and 1.5–2 °C or higher in calluses. We have validated our predictions on gelatin phantoms and demonstrated the feasibility of thermographic imaging for callus identification in two clinical case series. Our experimental results are in agreement with theoretical predictions and support the notion that local skin temperature variations can indicate epidermis thickness variations, which can be used for callus identification. In particular, a surface temperature drop on the order of 0.5 °C or more can be indicative of callus presence, particularly in callus-prone areas. In addition, our analytical calculations and phantom experiments show the importance of ambient temperature measurements during thermographic assessments.