Serum albumin level, in association with serum interleukin-6 level, is a significant prognostic factor in multiple myeloma patients. The aim of this study was to determine any clinical factors associated with decreased serum albumin level. We retrospectively reviewed the records of 373 patients diagnosed with multiple myeloma at the Asan Medical Center, Seoul, Korea, between January 1996 and March 2008. Patients were divided into two groups according to serum albumin level (above or below 3.5 g/dL, the prognostic cutoff value), and clinical parameters were compared between groups. We aimed to identify any clinical parameters associated with low serum albumin levels. The group with serum albumin <3.5 g/dL showed older patient age, lower hemoglobin level, and poorer performance status. By contrast, levels of serum beta(2)-microglobulin, serum M protein, and bone marrow plasma cells were significantly higher in the group with low serum albumin levels. No significant between-group differences were found when serum calcium and creatinine levels were compared. Numbers of cytogenetic abnormalities and lytic bone lesions also showed no significant between-group differences. In both univariate and multivariate analyses, serum albumin level less than 3.5 g/dL was identified as a significant pretreatment prognostic factor. Lower serum albumin levels in multiple myeloma patients are associated with clinical factors reflecting disease severity.