Monoclonal gammopathy of undetermined significance (MGUS) is a necessary precursor of multiple myeloma (MM). Compared with non-Hispanic White (White) patients, African American individuals experience approximately twofold greater, and Asian American individuals 50% lower, occurrence of MGUS and MM. We examined determinants of MGUS among Japanese American, African American, Latino, Native Hawaiian, and White participants in a case-control study nested in the Multiethnic Cohort (MEC) study. Presumptive cases included MEC participants aged ≥65 years initially screened using the Medicare billing code for paraproteinemia along with those diagnosed with MM or another plasma cell neoplasm at least 1 year after blood draw. Presumptive controls had no Medicare paraproteinemia billing code or MM. Laboratory confirmation resulted in 426 confirmed MGUS cases (370 non-immunoglobulin M [non-IgM] and 56 IgM) and 863 MGUS-free controls. We used multivariable logistic regression to estimate associations with MGUS. The distribution of immunoglobulin isotypes differed by race/ethnicity (P = .005): Japanese American individuals had the lowest (11.0%) and Native Hawaiian individuals the highest (23.5%) proportion of IgA. Each unit increase in body mass index (BMI; kilogram per square meter) was associated with a 6% increase in non-IgM MGUS (95% confidence interval, 3-9) among all racial/ethnic groups combined. BMI was also significantly associated within most racial/ethnic groups, especially among Native Hawaiian individuals (13% increase per BMI unit), with IgA and IgG MGUS, and with high and low risk MGUS. BMI was the main determinant associated with MGUS. Isotype distribution differed between racial/ethnic groups.