Abstract Rationale Multiple myeloma (MM) cells synthesize large amounts of paraproteins, making radiolabeled amino acids promising candidates for PET imaging of MM patients. Methods We compare tumor uptake of the two amino acid analogs [¹⁸F]-fluoroethyltyrosine and [¹⁸F]-FACBC in a MM xenograft model and show the feasibility of PET imaging with [¹⁸F]-FACBC in a MM patient. Results Preclinically [¹⁸F]-FACBC showed superior performance, mainly due to the uptake via the ASC-system. In a subsequent proof-of-concept investigation [¹⁸F]-FACBC PET was performed in a MM patient. It allowed identification of both lesions with and without CT correlate (SUVmean 8.0 or 7.9) based on higher uptake compared to normal bone marrow (SUVmean 5.7). Bone signal was elevated compared to non-MM patients, and, thus [¹⁸F]-FACBC potentially allows the assessment of bone marrow infiltration. Conclusion The FDA/EMA approved PET agent [¹⁸F]-FACBC is promising for imaging MM and should be further evaluated in prospective clinical studies.