BACKGROUND: Cancers of the head and neck are associated with detriments in health-related quality of life (HRQOL); however, little is known about different experiences between African Americans and non-Hispanic whites. METHODS: HRQOL was measured by the Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N) approximately 5 months postdiagnosis among 222 patients with cancer from North Carolina. Higher scores represent better HRQOL. Regression models included sociodemographic characteristics and clinical factors. RESULTS: African Americans reported higher physical well-being than whites (adjusted means, 23.1 vs 20.9). African Americans with incomes <$20,000 reported higher emotional well-being (21.4) and fewer head and neck symptoms (22.0). Non-Hispanic whites making <$20,000 reported the poorest emotional well-being (17.3), whereas African Americans making >$20,000 reported the most head and neck symptoms (18.7). CONCLUSIONS: Further investigation is needed to explore variation in HRQOL experiences among different race and socioeconomic groups that may inform resource allocation to improve cancer care.