© 2015 American Cancer Society. Background Health-related quality of life (HRQOL) heterogeneity among cancer survivors may mask subgroups (classes) with different limitations and long-term outcomes. The authors determined the HRQOL classes that exist among lung cancer survivors, examined transitions among those classes over time, and compared survival outcomes of patients according to the classes present in the initial phase of care. Methods Lung cancer survivors in the Cancer Care Outcomes Research and Surveillance Consortium completed EuroQol 5-domain quality-of-life questionnaires 4.8 months (initial phase) and >1 year (survivorship phase) after diagnosis (n = 1396). Latent class analysis and latent transition analysis were used to determine HRQOL classes and transitions across time. Correlates of class membership were tested using multinomial logistic regression. Kaplan-Meier and Cox regression analyses were used to compare survival across class membership. Results Latent class analysis identified 4 classes at diagnosis and follow-up: 1) poor HRQOL, 2) pain-dominant impairment, 3) mobility/usual activities impairment, and 4) good HRQOL. Probabilities of remaining in the same class were.87,.85,.82, and.73 for classes 4, 1, 3, and 2, respectively. Younger age, lower income, lower education, comorbidities, and a history of depression/emotional problems were associated with a greater likelihood of being in classes 1, 2, or 3 at follow-up. Patients in classes 1 and 3 had significantly lower median survival estimates than patients in class 4 (4.8 years, 3.8 years, and 5.5 years, respectively; P < .001). Conclusion Examining the heterogeneity of HRQOL in lung cancer populations allows the identification of classes with different limitations and long-term outcomes and, thus, guides tailored and patient-centered provision of supportive care. Cancer 2015;121:1520-1528.