del(17p13)(TP53) seems to be an independent poor prognostic factor in patients with relapsed/refractory multiple myeloma (MM) receiving lenalidomide. However, whether aberrant p53 nuclear expression detected by immunohistochemical analysis can be used as a surrogate marker for del(17p13)(TP53) in prognostic evaluation of lenalidomide-treated relapsed/refractory MM remains unclear. The p53 expression in myeloma cells from 88 patients was evaluated by immunohistochemical analysis, and 17p13(TP53) gene status was examined by fluorescence in situ hybridization (FISH). FISH detected hemizygous del(17p13)(TP53) in 13 (15%), and immunohistochemical analysis detected p53 nuclear expression in 11 cases (13%). del(17p13) (TP53) and p53 expression were strongly correlated (P < .0001). Furthermore, patients with aberrant p53 nuclear expression had significantly shorter progression-free and overall survival than patients without this abnormality. Our results suggest that p53 nuclear expression is associated with adverse outcome in patients with relapsed/refractory MM receiving lenalidomide-based therapy and that p53 immunohistochemical analysis may serve as a simple, rapid method to predict del(17p13)(TP53) in this patient subgroup.