BACKGROUND AND PURPOSE: Radiation dermatitis (RD) is often experienced by cancer patients undergoing radiation therapy (RT) and can negatively impact the quality of life of patients. The Skindex-16 questionnaire is an instrument that measures the impact of skin conditions on patient quality of life. The Skindex-16 has been validated for use in assessing many benign conditions, however it has not yet been validated for the assessment of patient-reported outcomes (PROs) for patients experiencing RD. MATERIALS AND METHODS: A group of 42 breast cancer patients enrolled in a StrataXRT study for RD were analyzed. Increases in Skindex-16 scores indicate worsening symptoms. To validate the Skindex-16, scores were compared at baseline, 2 weeks, and 3 months post-RT. Skindex-16 scores were also compared to scores from the Common Terminology Criteria of Adverse Events (CTCAE) for RD and the Radiation-Induced Skin Reaction Assessment Scale (RISRAS) using various statistical analyses at baseline, 2 weeks, and 3 months post-RT. RESULTS: Skindex-16 scores were found to be low at baseline and 3 months post-RT but peaked at 2 weeks post-RT. Significant worsening scores from baseline to 2 weeks post-RT were found in a longitudinal assessment of Skindex-16 items for several items on the patient portion of the RISRAS, but only two items on the healthcare professional RISRAS component. Skindex-16 scores showed no significant relationship to CTCAE scores. CONCLUSION: This validation of the Skindex-16 questionnaire indicates that it is reliable to be used for the assessment of PROs for cancer patients experiencing RD. However, the PROs assessed by Skindex-16 do not correlate with clinician-reported outcomes.