Context: Adolescents with differentiated thyroid cancer (DTC) require lifelong monitoring with a high possibility of reoperation or radioactive iodine. Although adult DTC survivors have similar or slightly worse quality of life (QOL), this has not been evaluated in the pediatric population. Objective: Our objective was to compare QOL and anxiety in adolescents with DTC to patients with acquired autoimmune hypothyroidism. Design, Setting, and Patients: In this cross-sectional pilot study, three validated questionnaires were administered to 16 adolescents with DTC and 16 controls for assessment of QOL and anxiety levels. These included teen and parent PedsQL, Multidimensional Anxiety Scale for Children, and Coddington Life Events Scales for Adolescents. The contribution of age, time since diagnosis, and biochemical variables were compared with the outcome measures. Results: There were 16 DTC patients (seven males); 13 had papillary carcinoma, one had follicular carcinoma, and two had mixed type. At diagnosis, five DTC patients had lymph node involvement and two had lung metastases, although at time of assessment, only one DTC patient had lymph node involvement. DTC patients were older than control subjects (P = 0.004) and had lower TSH levels than control subjects at time of assessment (P = 0.013). QOL and anxiety levels did not differ between DTC patients compared with control subjects and with previously reported scores in a healthy cohort.QOLand anxiety level parameters were not influenced by age, time since diagnosis, or free T4 levels measured at the time of assessment. Conclusions: Adolescents with DTC have similar QOL and anxiety levels compared with autoimmune hypothyroidism patients and with a healthy normative population.