Knowledge about species compatibility is crucial for proper interpretation of data from in vivo experiments with human proteins in pharmacological models and of data from cross-species in vitro experiments. Information about the cross-species compatibility of tissue factor (TF) and coagulation factor (F) VII (FVII) has accumulated since the early history of coagulation research. Many observations were connected to the introduction and development of the prothrombin time (PT) assay where fibrin clot formation was observed when tissue extracts of different origins were added to recalcified human or non-human plasmas. Studies on cross-species TF-FVIIa compatibility entered into a new area with the cloning and recombinant expression of TF and FVII from a number of species as well as with the possibility of specific amino acid substitution. TF and/or FVIIa from cattle, dog, rabbit, mouse, rat and zebrafish have been purified and characterized in varying detail. In addition to adding knowledge about the species-specific TF-FVIIa interactions, cross-species studies often reveal information which adds to the general view of the structural and functional properties of the human TF-FVIIa complex. This review briefly outlines the features of human TF and FVIIa, their intermolecular interactions, and the biological effects of TF-FVIIa complex formation and compares this information to findings obtained in studies addressing TF or FVIIa of non-human origin. By examples we point to difficulties which may arise from the transcendence across species borders and how some cross-species data have advanced our understanding of the structure and function of the human TF-FVIIa complex.