Following the advent of mechanical thrombectomy, occlusive clots in ischemic stroke have been amply characterized using conventional histopathology. Many studies have investigated the compositional variability of thrombi and the consequences of thrombus composition on treatment response. More recent evidence has emerged about the spatial heterogeneity of the clot or the preferential distribution of its components and compact nature. Here we review this emerging body of evidence, discuss its potential clinical implications, and propose the development of adequate characterization techniques.