To investigate whether geographic and cultural factors influence the relationship between the global health status quality of life (QL) scale score of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire and seven other subscales representing fatigue, pain, physical, role, emotional, cognitive, and social functioning. A large international database of QLQ-C30 responses was assembled. A linear regression model was developed predicting the QL scale score and including interactions between geographical/cultural groupings and the seven other scale scores. The pain subscale appeared to have relatively greater influence and fatigue relatively lower influence for those from other European regions compared with respondents from the UK when predicting overall quality of life (QoL). For Scandinavia physical functioning appeared to contribute relatively less. There was evidence of greater emphasis on cognitive functioning for those from South Asia and Latin America compared with the UK, whereas for those from Islamic countries, the role functioning scale appeared to have less influence and physical and social functioning more influence. These results provide evidence that different cultural groups may emphasize different aspects of their QoL. This has implications for studies using QoL questionnaires in international comparisons.