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To estimate health limitations and health-related quality of life (HRQL) associated with cancer and other chronic conditions in a nationally representative sample within a phase-of-care framework.We used a nested case–control design to assess health limitations and HRQL in individuals reporting a breast, colorectal, prostate, or lung cancer diagnosis, or a diagnosis of arthritis, diabetes, heart disease, or hypertension compared with similar controls without these conditions. All subjects were selected from the 1986–1994 National Health Interview Surveys linked to mortality files in 1995, and classified into the initial, continuing, or last year of life phase of care. Health limitations and HRQL were compared for cases and controls for each condition with 2-sided statistical tests.Across all conditions, individuals in the last year of life phase of care reported greater health limitations and lower HRQL, as measured by the Health Activities and Limitations Index (HALex), than did individuals in the initial and continuing phases of care. Compared with their matched controls, individuals with cancer or other chronic conditions were more likely to report health limitations and lower mean HALex values in the initial, continuing, and last year of life phases of care (P < 0.05).We observed greater health limitations and lower HRQL associated with cancer and other chronic diseases compared with similar individuals without these conditions. The phase-of-care framework used in this study seems to be applicable to the assessment of HRQL for cancer and other chronic diseases.