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BACKGROUND Adolescents and early young adults (AYAs) with cancer are at high risk for poor outcomes. Positive psychological responses such as benefit-finding may buffer the negative impacts of cancer but are poorly understood in this population. OBJECTIVE We aimed to prospectively describe the content and trajectory of benefit- and burden-finding among AYAs to develop potential targets for future intervention. PATIENTS AND METHODS One-on-one semistructured interviews were conducted with English-speaking AYA patients (aged 14-25 years) within 60 days of diagnosis of a noncentral nervous system malignancy requiring chemotherapy, 6-12 and 12-18 months later. Interviews were coded using directed content analyses with a priori schema defined by existing theoretical frameworks, including changed sense of self, relationships, philosophy of life, and physical well-being. We compared the content, raw counts, and ratios of benefit-to-burden by patient and by time point. SETTING/SUBJECTS Seventeen participants at one tertiary academic medical center (mean age 17.1 years, SD = 2.7) with sarcoma (n = 8), acute leukemia (n = 6), and lymphoma (n = 3) completed 44 interviews with >100 hours of transcript-data. RESULTS Average benefit counts were higher than average burden counts at each time point; 68% of interviews had a benefit-to-burden ratio >1. Positive changed sense-of-self was the most common benefit across all time points (44% of all reported benefits); reports of physical distress were the most common burden (32%). Longitudinal analyses suggested perceptions evolved; participants tended to focus less on physical manifestations and more on personal strengths and life purpose. CONCLUSIONS AYAs with cancer identify more benefits than burdens throughout cancer treatment and demonstrate rapid maturation of perspectives. These findings not only inform communication practices with AYAs but also suggest opportunities for interventions to potentially improve outcomes.