We investigated the relevance of p53 deletions to the clinical outcome of patients with multiple myeloma (MM) treated with high-dose chemotherapy and autologous stem cell transplantation. Hemizygous p53 gene deletions were detected by fluorescence in situ hybridization in 10 of 105 (9.5%) patients studied. p53 deletions were associated with higher serum calcium (P = .0062) and creatinine (P = .013) levels, but there were no association with patient age, gender, beta2-microglobulin, C-reactive protein, hemoglobin, albumin or bone lytic lesions, or immunoglobulin isotype. There were no associations of p53 deletions with 13q deletions or translocations t(11;14) or t(4;14). Patients with p53 deletions had significantly shorter progression-free (median, 7.9 versus 25.7 months, P = .0324) and overall survival (median, 14.7 versus 48.1 months, P = .0008) than patients without a p53 deletion. A multivariate analysis confirmed p53 deletion was an independent prognostic factor predicting shortened progression-free (P = .0009) or overall survival (P = .0002) in patients with MM after high-dose chemotherapy and autologous stem cell transplantation.