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We investigated the prognostic value of the magnetic resonance imaging (MRI) pattern of bone marrow involvement in patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). 126 patients with untreated MM indicated for ASCT underwent spine MRI and cytogenetic analysis at diagnosis. All patients received ASCT after induction therapy of VAD (vincristine, doxorubicin, dexamethasone; n = 55) or a thalidomide-based regimen (TCD; n = 71). Thalidomide maintenance therapy was performed in 68 patients. The MRI pattern was normal in 27, focal in 47, and diffuse/variegated in 52 patients. Patients with the diffuse/variegated pattern showed significantly higher stage (P = 0·038), higher β-2 microglobulin level (P = 0·001) and severe anaemia (P = 0·015). However, the cytogenetics were not different among the MRI patterns (P = 0·890). Progression-free survival (PFS) was lower in the diffuse/variegated pattern (P = 0·002) than other patterns, but not overall survival (OS) (P = 0·058). Thalidomide maintenance therapy was correlated only with PFS (P = 0·001). High-risk cytogenetics were associated with both poorer PFS (P < 0·001) and OS (P = 0·003). In a multivariate analysis, the diffuse/variegated MRI pattern was an independent predictor of disease progression (Hazard Ratio, 1·922; 95% confidence interval, 1·185–3·118; P = 0·008). The diffuse/variegated MRI pattern is a novel prognostic factor for disease progression in MM patients eligible for ASCT.