Monoclonal gammopathy of undetermined significance (MGUS), is a pre-malignant plasma cell disorder that affects roughly 4% of the population older than 55 and is associated with a 1% per year risk of progression to multiple myeloma (MM). Successfully intercepting disease progression from MGUS to MM requires a deeper understanding of MGUS biology, identification of prognostic biomarkers and potential targets for interception. With these aims, a cohort of samples were profiled from the Olmstead County Study, which followed >20,000 subjects for over 20 years as they aged and developed a variety of diseases, including MGUS and MM (Kyle, et al. Oncology 2011). Samples were utilized from 2 cohorts: 1) healthy normal individuals with no subsequent diagnosis of plasma cell disorder, and 2) healthy normal individuals who go on to develop MGUS, with a second sample at the time of MGUS diagnosis. Broad proteomic profiling was performed on these samples, to identify pathways involved in the early stages of MGUS disease biology.