The purpose of this study was to clarify the cross-cultural validity of the relationship between innovation, entrepreneurial orientation (EO), and performance in five different countries: China, Germany, The Netherlands, Peru, and Russia. We found that innovation and EO are effective in each country, suggesting universal relationships. At the same time, both national culture and cultural orientations of owners moderated the relationship between innovation and performance. We conclude that entrepreneurship research needs to address culture in order to test the boundaries of theory. Additionally, cross-cultural entrepreneurship research needs to study multiple levels of culture.