Efficient differentiation of embryonic stem cells (ESCs) and induced pluripotent Factor Xa stem cells (iPSCs) to various lineages involves step-wise approaches replicating the important thing commitment stages found in the course of embryonic growth. Here we display that expression of PdgfR-alpha segregates mouse ESC-derived Flk-1 mesoderm into Flk-1(+)PdgfR-alpha(+) cardiac and Flk-1(+)PdgfR-alpha(-) hematopoietic subpopulations. By monitoring Flk-1 and PdgfR-alpha expression, we discovered that specification of cardiac mesoderm and cardiomyocytes is established by maybe remarkably little alterations in amounts of Activin/Nodal and BMP signaling. Translation to human ESCs and iPSCs revealed that the emergence of cardiac mesoderm could also be monitored by coexpression of KDR and PDGFR-alpha and that this approach was similarly dependent on optimal ranges of Activin/Nodal and BMP signaling. Importantly, we found that person mouse and human pluripotent stem cell lines call for optimization of these signaling pathways for productive cardiac differentiation, illustrating a principle that may well apply in other contexts.