Antibodies that specifically bind the extracellular domain of IRTA2 are disclosed herein. In one embodiment, these antibodies do not specifically bind IRTA1, IRTA3, IRTA4, or IRTA5. In one example, the antibodies are humanized antibodies. The antibodies can be conjugated to effector molecules, including detectable labels, radionucleotides, toxins and chemotherapeutic agents. The antibodies that specifically bind IRTA2 are of use to detect B cell malignancies, such as hairy cell leukemia and non-Hodgkin's lymphoma. These antibodies that specifically bind IRTA2 are also of use to treat B cell malignancies that express IRTA2, such as hairy cell leukemia and non-Hodgkin's lymphoma.