Cross-cultural psychology, in both its culture-comparative and its cultural traditions, has been a highly successful enterprise; it has been instrumental in establishing context variation as an essential factor in the study of behavior and has led to a large volume of publications with culture as a key term. At the same time, the question arises whether the further accumulation of findings of often small differences between groups will continue to be a worthwhile pursuit, or whether it is time for a reorientation. Here two widespread assumptions of research on behavior and culture are discussed that are likely to be unsustainable: (i) a focus on cross-cultural differences at the cost of cultural invariance, (ii) the presumed psychological coherence of cultures, especially national cultures, reflected in major dimensions of differences in psychological functioning. It is argued that also emerging methods in cultural neuropsychology continue to place too much emphasis on cross-cultural differences and cultural coherence. With a view to reorientation two ideas are explored: (i) culture-comparative research needs an explicit focus on what humans as a species have in common (psychological invariance) and (ii) explanatory frameworks should have a better theoretical foundation. Research traditions in biology are mentioned that can provide a source of inspiration to researchers in cross-cultural psychology. One such tradition is classical ethology as outlined by Tinbergen (1963) who proposed that in the analysis of behavior patterns researchers should be asking multiple questions about the immediate context (cause), function, ontogenetic development and phylogenetic history.