SIGNIFICANCE: Mueller matrix (MM) polarimetry is a promising tool for the detection of skin cancer. Polarimetric in vivo measurements often suffer from misalignment of the polarimetric images due to motion, which can lead to false results. AIM: We aim to provide an easy-to-implement polarimetric image data registration method to ensure proper image alignment. APPROACH: A feature-based image registration is implemented for an MM polarimeter for phantom and in vivo human skin measurements. RESULTS: We show that the keypoint-based registration of polarimetric images is necessary for in vivo skin polarimetry to ensure reliable results. Further, we deliver an efficient semiautomated method for the registration of polarimetric images. CONCLUSIONS: Image registration for in vivo polarimetry of human skin is required for improved diagnostics and can be efficiently enhanced with a keypoint-based approach.