To molecularly characterize the rare and aggressive tumors known as angiosarcomas, Chan et al utilized a combination of transcriptomic immuno-oncology profiling with multiplex immunohistochemistry and immunofluorescence. HALO image analysis software was used for the quantification of PD-L1, CD68, CD8, FOXP3, CD15, and ERG. From these studies, three phenotypes of patients were identified according to etiology, anatomical origin, signaling pathways, and the tumor inflammation signature. These distinct biological phenotypes provide opportunity for future studies to improve prognosis and treatment of a rare and deadly disease.