The extracellular matrix protein fibronectin contains a domain that is rarely found in healthy adults and is almost exclusively expressed by newly formed blood vessels in tumours, particularly in solid tumours, different types of lymphoma and some leukaemias. This domain, called the extra domain B (ED‐B), thus has broad therapeutic potential. The antibody L19 has been developed to specifically target ED‐B and has shown therapeutic potential when combined with cytokines, such as IL‐2. In this review article, we discuss the preclinical research and clinical trials that highlight the potential of ED‐B targeting for the imaging and treatment of various types of cancer. ED‐B‐centred studies also highlight how proper patient stratification is of utmost importance for the successful implementation of novel antibody‐based targeted therapies. The extracellular matrix protein fibronectin contains a domain that is rarely found in healthy adults and is almost exclusively expressed by newly formed blood vessels in tumours, the extra domain B (ED‐B). This review summarizes preclinical research and clinical trials on the potential of antibody‐based ED‐B targeting for tumour visualization and treatment.