BACKGROUND: Instruments are needed to measure the influence of cancer on quality of life in the expanding population of long-term cancer survivors. We conducted refinement and psychometric evaluation of the Impact of Cancer (IOC) scale by use of data from a large sample of long-term breast cancer survivors and developed an instrument, the Impact of Cancer version 2 (IOCv2), to measure quality of life outcomes. METHODS: Questionnaires including 81 potential IOC scale items, the Center for Epidemiologic Studies-Depression (CES-D) scale, and the Breast Cancer Prevention Trial (BCPT) symptom scales, as well as demographic, treatment, and medical information, were completed by 1188 disease-free breast cancer survivors 5-10 years after diagnosis. We used exploratory factor analysis to identify scales and assessed reproducibility by split-sample cross-validation. Higher-order scales were extracted and all scales were evaluated for internal consistency and construct and concurrent validity. RESULTS: The analysis yielded a factor structure relating IOC items to psychosocial impact domains that exhibited high factor loadings (factor-item correlations of 0.59-0.94), high internal consistency (Cronbach’s alpha statistics of 0.76-0.89), and a total congruence of 0.98 across the split samples. The Impact of Cancer version 2 (IOCv2) scales consist of a Positive Impact Summary scale with four subscales (Altruism and Empathy, Health Awareness, Meaning of Cancer, and Positive Self-Evaluation), a Negative Impact Summary scale with four subscales (Appearance Concerns, Body Change Concerns, Life Interferences, and Worry), and subscales for Employment and Relationship Concerns. Patterns of association between IOCv2 scale scores and CES-D and BCPT scores indicated good concurrent validity. Patterns of associations between IOCv2 scale scores and demographic, medical, and treatment characteristics indicated good construct validity. CONCLUSION: The IOCv2 scales provide a validated tool for measuring the impact of cancer on quality of life in long-term cancer survivors.