Background: In the Western world, it is widely accepted as natural – and seen almost as a law of nature – that mankind is divided into two sexes or genders – males and females. In many cultures and societies, however, more than two sex and/or gender categories are recognized, which in some instances refer to the biological sex and in others to gender roles and social status. Aims: To give an intercultural comparison of various ways of dealing with gender variance. Methods: In the following paper, we review the anthropological literature during the last 100 years describing individuals who live neither as men nor women in various non-Western cultures. Results: Only rarely, these individuals suffer from disorders of sex development in the modern medical or biological definition: in many if not all societies there have been individuals who are not covered by the gender category of male and female. Conclusion: There thus appears to be a cultural need for people with a special neither-male-nor-female status, which might be classified as ‘gender variance’.