Purpose: Quality of life (QOL) is increasingly recognized as a critical cancer-treatment outcome measure, but little is known about the impact of QOL on the patient decision-making process. A pilot study was conducted in an effort to (1) measure the expectations of patients, physicians, and research nurses regarding the potential benefits and toxicities from experimental and standard therapies, and (2) determine the relationship of QOL to patient perceptions regarding treatment options. Methods: Thirty cancer patients enrolling in phase I clinical trials, their physicians, and their research nurses were administered questionnaires that assessed demographics, QOL, and treatment expectations. Results: Compared with their physicians, patients overestimated potential benefits and toxicities from experimental therapy (mean expected benefit, 59.8% v 23.8%, P < .01; mean expected toxicity, 29.8% v 16.0%, P < .01). Patients estimated a greater potential for benefit (59.8% v 36.8%, P < .01) and less potential for toxicity (29.8% v 45.6%, P = .01) for experimental therapy, compared with standard therapy. Short Form-36 general health perception correlated with patient perception of potential benefit from experimental therapy (r = .48, P = .01). Conclusion: Participants in phase I clinical trial have high expectations regarding the success of experimental therapy and discount potential toxicity. Patient QOL may affect the expectation of benefit from experimental therapy and, ultimately, treatment choice. Understanding the interactions between QOL and patient expectations may guide the development of improved strategies to present appropriate information to patients considering early-phase clinical trials.