Few risk factors have been established for the plasma cell disorder multiple myeloma, but some of these like African American ethnicity and a family history of B-cell lymphoproliferative diseases suggest a genetic component for the disease. Genetic variation represents the genetic basis of variability in a population. The complex interplay between environment and genes for the development of cancer may therefore be influenced by genetic variations. A genetic variation may change the function of the gene, and if the genetic variation is associated with the risk of disease, that particular gene may be involved in the pathogenesis of disease. Genes of interest are genes involved in the normal development and function of the plasma cell and genes that protect us against exposures from the environment, for example, genes involved in the metabolism of xenobiotics, metabolism of folate and methionine, as well as genes involved in inflammation and DNA repair. Identification of genes with potential influence on cancer risk may help us to establish relevant laboratory studies on exposure and dose-response assessment and may help us to test the hypothesis in epidemiological studies. Knowledge of individual at high risk of cancer may offer promising insight for the prevention of cancer.