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PURPOSE: Research in the area of cultural response pattern on questionnaires in the oncological setting and direct cross-cultural comparisons are lacking. This study examined response pattern in the reporting of depressive symptoms in Chinese and US women with breast cancer. We hypothesized that Chinese women are less likely to endorse positive affect items compared to their US counterparts. Additionally, we explored cultural differences in the association between positive affect and QOL. METHODS: Secondary analyses of baseline assessments of two mind-body intervention studies for women with breast cancer undergoing radiotherapy in the USA (N = 62) and China (N = 97) are presented. All participants completed measures of depressive symptoms (CES-D) and cancer-specific QOL (FACT-B). We examined cultural differences on positive and negative affect items on the CES-D. RESULTS: Controlling for demographic factors, ANCOVA revealed a significant cultural difference in positive (F = 7.99, p = 0.005) but not negative affect (p = 0.82) with Chinese women reporting lower positive affect compared to US women (Chinese = 6.97 vs. US = 8.31). There was also a significant cultural difference (F = 3.94, p = 0.03) in the association between positive affect and QOL so that lower positive affect was more strongly associated with worse emotional well-being in Chinese (beta = 0.57, p < 0.0001) than US women (beta = 0.35, p < 0.01). CONCLUSIONS: Chinese women reported lower positive affect compared to US women and lower levels of positive affect were more strongly associated with worse QOL. Special attention is needed when examining mental health in different cultures to ascertain effective delivery of clinical services to those in need.