BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors frequently result in dermatologic toxicities, including rash, xerosis, pruritus, and paronychia. Although the frequency and severity of these events have been described, their effect on health-related quality of life (QoL) remains poorly understood. By using a dermatology-specific questionnaire, the authors examined the effect of these toxicities on QoL. METHODS: Patients completed the Skindex-16, a questionnaire that measures the effects on 3 domains of QoL: symptoms, emotions, and functioning. The severity of dermatologic toxicities was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 (NCI-CTCAE). Correlations of dermatology QoL scores with NCI-CTCAE grade, skin phototype (SPT), sex, age, type of EGFR inhibitor, and cancer type were investigated. RESULTS: Concordant with greater severity of rash grade, there was an increase in median scores for symptoms (P ¼ .0006), emotions (P < .0001), function (P ¼ .001), and overall score (P < .0001). There was an inverse correlation between age and emotions (r ¼ À0.26; P ¼ .03) and overall score (r ¼ À0.25; P ¼ .04). There was a significant difference between patients aged 50 years and patients aged >50 years with regard to symptoms (P ¼ .02), emotions (P ¼ .03), functioning (P ¼ .04), and overall score (P ¼ .02). There were no significant differences between QoL and SPT, sex, treatment type, or cancer type (P > .05). CONCLUSIONS: Toxicities, including rash, xerosis, paronychia, and pruritus, adversely affected QoL, and rash was associated with a QoL greater decrease. Younger patients reported lower overall QoL than older patients who had the same toxicities. The current results support using the NCI-CTCAE as a correlative tool for measuring the effects of rash on dermatology-specific QoL. Cancer 2010;116:3916-23.