This study is concerned with ways in which children with Williams syndrome (WS), a rare neurodevelopmental disorder arising from a hemizygous deletion in chromosome band 7q11.23 including the gene for elastin (ELN) and approximately 20 surrounding genes, are affected by social mores of vastly differing cultures: the United States and Japan. WS presents a compelling model for the investigation because its genetic phenotype is well defined and results in an uneven cognitive profile as well as a social phenotype typical of the syndrome including overt over-friendliness toward strangers. While a number of research groups have been studying the cognitive strengths and weaknesses of individuals with WS in various countries, there have not been studies to date that explore the social phenotype in WS across different cultures. This study examines the ways in which social behavior in WS, stemming from specific genetic underpinnings, might be mediated by cultural expectations. We conducted a cross-cultural study using an instrument that measures aspects of sociability commonly found among people with WS. Quantitative analyses revealed a significant effect of diagnostic category in that in both countries, children with WS were rated as significantly higher in global sociability and more likely to approach strangers than were their normal counterparts. There was also an effect of culture, in that regardless of category, WS and normal children in Japan were rated lower than their counterparts in the US. We suggest that the excessively social phenotype of children with Williams syndrome, although markedly present across cultures, appears to vary in its intensity by culture. This is an intriguing illustration of interactions between nature and nurture.