Harnessing the cancer-specific antibody repertoire of cancer patients using the methodology described herein may also potentially offer an alternate strategy to yield IgG antibodies against cancer antigens. Recent advances reported by Traggiai et al., evaluating monoclonal antibodies from human memory B cells have yielded fully-human virus-neutralizing antibodies of therapeutic relevance for infectious diseases and have contributed to the dissection of humoral memory responses to vaccinations [35, 57, 58] . Here, we focus on B cells from cancer patients such as melanoma patients, analyze systemic humoral responses to cancer and demonstrate the presence of tumor-reactive and tumorspecific antibodies. This approach may offer an advantage over other approaches such as phage display in that it yields in vivo affinity-matured human antibodies with naturally paired heavy and light chains. The patient-derived monoclonal antibody 6_2G3 bound to 2 out of 6 of the melanoma cell lines evaluated compared to melanocytes, suggesting that this antibody may be against a protein over-expressed or mutated on the surface of cancer cells. In light of the efficacy of Trastuzumab, against the HER2/neu antigen expressed on 20-30% of breast cancers, as a clinicallyvalidated therapeutic tool for the treatment of an equivalent proportion of breast cancer patients [59] , selection of antibodies that bind to a portion of cell lines may merit further characterization. Although the clinical significance of mature memory B cells expressing antibodies that recognize tumor cells in patients remains to be elucidated, antibodies derived from these cells, introduced by passive immunotherapy in therapeuticallyrelevant doses, such as those used for Trastuzumab to patients with breast cancer, merit investigation for any potential relevance in melanoma. Other potential future benefits of screening patientderived B cells from tumor-reactive antibodies may be identification of novel cell surface tumor antigens. Future evaluations of clone 6_2G3 will include sequence analysis and expression cloning to allow for further analyses of specificity to melanoma tumors, antigen identification, and for thorough functional assessments.