This article presents a discussion of the principle of extracortical organization of higher mental functions and its significance for the development of contemporary neuropsychology. The role of external factors (stimulus-mediator, symbol) in establishing functional connections between various brain systems is, in principle, universal. However, inasmuch as differing mediators and means, or significantly different details within them (direction of writing, orientation by maps or by the behavior of sea birds, etc.) may and in fact do develop in different cultures, neuropsychological analysis must take into account cross-cultural differences. Diagnostic tools must also be adapted to differing cultural contexts. The efficacy of this principle for the analysis of bilingual aphasia and of mental organization of speech, including the effect of acquisition of literacy in native language, is demonstrated. The importance of this principle for the development of new directions in applied neuropsychology is also discussed.