The paper aims at proposing an extended notion of epigenesis acknowledging an actual causal import to the phenotypic dimension for the evolutionary diversification of life forms. “Introductory remarks” section offers introductory remarks on the issue of epigenesis contrasting it with ancient and modern preformationist views. In “Transmutation of forms: phenotypic variation, diversification, and complexification” section we propose to intend epigenesis as a process of phenotypic formation and diversification dependent on environmental influences, independent of changes in the genomic nucleotide sequence, and (...) occurring during the whole life span. Then, “Evolvability and phenotypic evolution” section focuses on phenotypic plasticity and offers an overview of basic properties that allows biological systems to be evolvable—i.e. to have the potentiality of producing phenotypic variation. Successively, the emphasis is put on environmentally-induced modifications in the regulation of gene expression giving rise to phenotypic variation and diversification. After some brief considerations on the debated issue of epigenetic inheritance, the issue of culture is considered. The key point is that, in the case of humans and of the evolutionary history of the genus Homo at least, the environment is also, importantly, the cultural environment. Thus, “Bio-cultural feedback” section argues that a bio-cultural feedback should be acknowledged in the “epigenic” processes leading to phenotypic diversification and innovation in Homo evolution. Finally, “Brain plasticity and cultural neural reuse” section introduces the notion of “cultural neural reuse”, which refers to phenotypic/neural modifications induced by specific features of the cultural environment that are effective in human cultural evolution without involving genetic changes. Therefore, cultural neural reuse may be regarded as a key instance of the bio-cultural feedback and ultimately of the extended notion of epigenesis proposed in this work. (shrink)