Purpose: To describe and compare the perceptions of cancer patients and their physicians regarding phase I clinical trials. Methods: Eligible patients had been offered phase I trial participation and had decided to participate but had not yet begun treatment. Each patient's physician also served as a study subject. Patients and physicians completed questionnaires with domains including perceptions of potential benefit and harm from treatment (experimental and standard), relative value of quality and length of life, and perceived content of patient-physician consultations. Results: Three hundred twenty-eight patients and 48 physicians completed surveys. Patients had high expectations regarding treatment outcomes (eg, median 60% benefit from experimental therapy), with those choosing to participate in a phase I trial being more optimistic than those declining phase I participation. Patients predicted a higher likelihood of both benefit and adverse reactions from treatment (experimental and standard) than their physicians (P < .0001 for all comparisons). Although 95% of patients reported that quality of life was at least as important as length of life, only 28% reported that changes in quality of life with treatment were discussed with their physicians. In contrast, 73% of physicians reported that this topic was discussed (P < .0001). Conclusion: Cancer patients offered phase I trial participation have expectations for treatment benefit that exceed those of their physicians. The discordant perceptions of patients and physicians may possibly be explained by patient optimism and confidence; however, the discrepancies in reports of consultation content, particularly given patients' stated values regarding quality of life, raise the possibility that communication in this context is suboptimal.