Cancer is a leading cause of death globally. Early detection of tumors can be an effective way to reduce mortality, however, traditional cancer diagnostic methods are based on the detection of organ dysfunction, which generally occurs at advanced stages of the disease. The first signs of disease initiation appear much earlier as molecular abnormalities yet are challenging to detect. An advanced design of microbubbles is reported that allows molecular targeting for subsequent binding to tumor cells. The microbubbles consist of perfluorocarbon gas encapsulated in a functional and stable shell made of a surface-active protein (hydrophobin HFBI from Trichoderma reesei) and corresponding fusion protein (HFBI-domZ) onto which antibodies can be easily grafted. The functionality of the bubbles is investigated, among others, using cryogenic transmission electron microscopy (cryo-TEM), confocal microscopy, and in vitro experiments. The results show the potential of the microbubbles as a probe to be used as a targeting contrast agent in ultrasound molecular imaging (MI) for cancer diagnostics.