Antigenic targets of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) paraproteins might play a role in the pathogenesis of these neoplasms. We screened a human fetal brain-derived macroarray with the IgA or IgG containing sera of 192 consecutive MGUS and MM patients. Twenty-nine of 192 (15.1%) paraproteins reacted with paratarg-7, a protein of unknown function which is expressed in all human tissues. Paratarg-7 reactivity was similarly frequent among IgA and IgG paraproteins, but all paratarg-7 reactive IgG paraproteins belonged to the IgG3 subtype with 24/57 IgG3 (42.1%) paraproteins displaying this specificity. Sequence analysis of paratarg-7 derived from patients having a paraprotein with specificity for paratarg-7 revealed no differences to paratarg-7 derived from patients with paraproteins of other specificities or healthy controls, excluding mutations or polymorphisms as a reason for its autoimmunogenicity. Similarly, Western-blot analysis showed identical bands for paratarg-7 derived from patients and controls. The above-random frequency of paratarg-7 as a paraprotein target suggests that paratarg-7 might be involved in the development of the respective clonal proliferations. The identification of paratarg-7 as an antigenic target enables the more detailed analysis of tumor-host interactions in these patients and their role in the pathogenesis of MM and MGUS.