Primitive endoderm (PrE)‐related cell lines (XEN, pXEN and nEnd cells) show key features of the PrE. By transcriptome analysis, we show: (a) Compared to embryonic stem cells, PrE‐related cell lines are less in vivo like, although early nEnd cells are most similar to the PrE. (b) These cell lines show post‐PrE features of parietal (XEN and pXEN cells) or visceral (nEnd cells) endoderm, likely driven by Tgf‐β and Wnt/Activin signaling, respectively. (c) pXEN and nEnd cell lines additionally show pre‐PrE features. Hence, neither pXEN nor nEnd cell cultures represent a distinct in vivo entity. Rather, their properties are compatible with mixed and hybrid phenotypes. Our findings indicate that pre‐PrE, PrE and early post‐PrE phenotypes result from different niches, which need to be better understood to derive cell lines that distinctly represent the early stages of the extraembryonic endoderm.