We report on the use of a fiber-based Mueller-matrix optical coherence tomography (OCT) system with continuous source-polarization modulation for in vivo imaging of early stages of skin cancer in SENCAR mice. A homemade hand-held probe with integrated optical scanning and beam delivering optics was coupled in the sample arm. The OCT images show the morphological changes in skin resulting from pre-cancerous papilloma formations that are consistent with histology, thus demonstrating the system’s potential for early skin cancer detection.