No medical tests are currently available to predict when an arterial plaque is at an imminent risk of rupturing and causing a heart attack or stroke. In a retrospective human clinical study of 50 heart attack cases and 44 controls, Damani et al. report that the presence of elevated levels of circulating endothelial cells could be used to correctly classify 86 of the 94 patients in the study (91.5%). The circulating endothelial cells were recovered with a commercially available system that isolates rare cells using magnetic nanoparticles coated with antibodies that recognize a cell surface protein. Additional automated analysis of images from fluorescently labeled cells from eight cases and ten controls revealed that the circulating endothelial cells from heart attack patients had distinctive morphologies. Taken together, these findings are consistent with a model in which injured arteries slough endothelial cells into the bloodstream. If detected, these rare cells could serve as predictive markers of a heart attack. (Sci. Transl. Med. 4, 126ra33, 2012)