When health-related quality of life instruments developed for and validated in 1 respondent group are completed by a different respondent group, findings could be invalid. The purpose of this study was to summarize the instrument outcomes when a widely used health-related quality of life instrument (the Health Utilities Index 3 [HUI3]) created from a population-based strategy was completed by pediatric oncology nurses for their patients during cancer treatment. Fifty-four nurses completed the HUI3 a total of 261 times at 1 to 3 sequential data points (106, 94, and 61, respectively) for pediatric patients who were enrolled on a frontline therapeutic clinical trial for acute lymphoblastic leukemia. Data were collected at 2 children’s hospitals. HUI3 scores could not be calculated for 52% to 61% of the nurse reports at each of the 3 data points because of nurses’ use of the "do not know" response option. Missing data of this proportion indicate that the nurse serving as a proxy rater independent of directly soliciting responses from the patient will not be able to rate certain attributes of the HUI3 more than half of the time despite having ongoing familiarity with the patient. Because of this, use of the HUI3 by nurse proxies for patients with pediatric acute lymphoblastic leukemia is not recommended.