Purpose: We observed that quality-of-life (QL) scores, collected to evaluate treatment in a randomized trial in advanced breast cancer, predicted survival duration. This report explores the prognostic associations between QL and survival in more detail. Patients and Methods: In a randomized clinical trial comparing intermittent and continuous therapy policies for patients with advanced breast cancer, QL was measured by linear analog self- assessment (LASA) and the Quality-of-Life Index (QLI). Baseline scores and subsequent changes were included in statistical models of survival duration, with and without other prognostic factors. Results: Physician assessment of QLI and patient LASA scores for physical well-being (PWB), mood, nausea and vomiting, appetite, and overall QL (but not pain) at the commencement of treatment were significant predictors of subsequent survival. Scores for PWB and QLI were independent of other prognostic factors. Changes in scores were also prognostically important. Both baseline and change in scores for PWB, mood, pain, and QLI after the first three treatment cycles, but before an arbitrary 180-day time point, were significantly predictive of survival beyond that time. Both QLI and PWB were prognostically independent of tumor response. Although QL improvement was correlated with tumor response, continuous therapy yielded significantly better QL scores, even in nonresponders. Conclusion: These findings support the validity of the simple QL measures used in the trial. They are compatible with the simple explanation that patients perceive disease progression before it is clinically evident, but also with a causal relationship between QL and survival duration.