A number of specific chromosomal abnormalities define the subgroups of multiple myeloma. In a meta-analysis of two genome-wide association studies of multiple myeloma including a total of 1 1,661 1 affected individuals, we investigated risk for developing a specific tumor karyotype. The t(1111;14)(q13;q32) translocation in which CCND1 is placed under the control of the immunoglobulin heavy chain enhancer was strongly associated with the CCND1 c.870G>A polymorphism (P = 7.96 × 1 10−1111). These results provide a model in which a constitutive genetic factor is associated with risk of a specific chromosomal translocation.