<p>To evaluate the role of FDG PET/CT before and after the treatment of multiple myeloma (MM) in our clinical practice, data from 32 patients (before therapy: 10 patients; after therapy: 22 patients) and from 46 examinations (before therapy: 10; after: 36) with a median time of follow-up of 24 months (before the therapy) and 26 months (after the therapy) were evaluated. FDG PET/CT positivity was characterized by SUVmax >2.5, SUVmax >4.2, focal lesions (FLs) >3, and presence of extramedullary disease (EMD). The median progression-free survival (PFS) and the median overall survival (OS) for FDG PET/CT positive patients were shorter than for negative patients, according to all parameters. Before the therapy, significant correlation was found only between PFS and the number of FLs (<em>p</em> = 0.033). After the treatment, significant correlation was found between PFS and SUVmax (cut-off value 2.5: p < 0.001; cut off value 4.2: p < 0.001), between PFS and the number of FLs (<em>p</em> = 0.009), and between PFS and the presence of EMD (p < 0.001). Significant correlation was found between OS and SUVmax (cut-off value = 2.5, <em>p</em> < 0.001 and 4.2, <em>p</em> = 0.009), between OS and the number of FLs (<em>p</em> = 0.007), and between OS and the presence of EMD (<em>p</em> = 0.022). Our results confirmed the reliability and good prognostic value of FDG PET/CT in MM.</p>