Mueller polarimetry imaging is gaining acceptance in diagnostic imaging as a potential tool for identifying tissue pathology by the integrated analysis of tissue response to polarized light. The Mueller matrix derived parameters have been related to the structural changes occurring in the tissues during pathogenesis of a disease. An in-house developed Mueller polarimetric imaging system has been explored in this study to differentiate between the normal and sclerodermic regions of unstained skin biopsy samples with varying collagen densities in the dermis. The optical response of excessive collagen deposition in scleroderma gets reflected in the depolarization, diattenuation, and retardance parameters obtained through polar decomposition and singular value analysis. In this study, higher depolarization, retardance and diattenuation values were observed in the scleroderma region as compared to their normal counterpart, suggesting an increased level of collagen deposition, which was further correlated with the histopathological findings. The developed system aims at its deployment in pathology labs to provide stain-free examination procedures in the long run. © 2019 SPIE.