Last edited 09/2022 and last reviewed 09/2022

Recommended tests for the diagnosis of myeloma and related organ dysfunction are as follows (1):

  • history and physical examinations

investigations recommended by British Committee for Standards in Haematology (BCSH)/UK Myeloma Forum (UKMF)

The UKMF/BCSH guidelines on the diagnosis and management of multiple myeloma recommends that investigation of a suspected myeloma patient should include screening tests followed by further tests to confirm the diagnosis (1).

Patients with suspected myeloma should be investigated using the tests listed (1):

  • screening tests FBC
  • urea & creatinine
  • calcium
  • immunoglobulins & serum electrophoresis
  • serum free light chains

A bone marrow biopsy should be undertaken in patients in whom there is a clinical concern for end organ damage and/or those with a significantly elevated monoclonal protein (M-protein)

NICE state (2):

  • use serum protein electrophoresis and serum-free light-chain assay to confirm the presence of a paraprotein indicating possible myeloma or monoclonal gammopathy of undetermined significance (MGUS)
  • if serum protein electrophoresis is abnormal, use serum immunofixation to confirm the presence of a paraprotein indicating possible myeloma or MGUS
  • do not use serum protein electrophoresis, serum immunofixation, serum-free light-chain assay or urine electrophoresis (urine Bence-Jones protein assessment) alone to exclude a diagnosis of myeloma

Tests to establish diagnosis

  • bone marrow aspirate + trephine biopsy with plasma cell phenotyping
  • immunofixation of serum and urine
  • skeletal survey

Tests to estimate tumour burden and prognosis

  • Fluorescence in situ hybridisation (FISH) analysis
  • quantification of monoclonal protein in serum and urine
  • albumin 2 - microglobulin
  • skeletal survey

NICE state with respect to prognostic information (2):

  • when performing a bone marrow aspirate and trephine biopsy to provide prognostic information:

    • perform fluorescence in-situ hybridisation (FISH) on CD138-selected bone marrow plasma cells to identify the adverse risk abnormalities t(4;14), t(14;16), 1q gain, del(1p) and del(17p)(TP53 deletion). Use these abnormalities alongside International Staging System (ISS) scores to identify people with high-risk myeloma
    • consider performing FISH on CD138-selected bone marrow plasma cells to identify the adverse risk abnormality t(14;20), and the standard risk abnormalities t(11;14) and hyperdiploidy
    • consider performing immunophenotyping of bone marrow to identify plasma cell phenotype, and to inform subsequent monitoring
    • consider performing immunohistochemistry (including Ki-67 staining and p53 expression) on the trephine biopsy to identify plasma cell phenotype and give an indication of cell proliferation, to provide further prognostic information
  • perform serum-free light-chain assay and use serum-free light-chain ratio to assess prognosis

Tests to assess myeloma related organ impairment (ROTI)

  • FBC
  • serum urea and creatinine
  • creatinine clearance (measured or calculated)
  • calcium albumin plasma viscosity
  • tissue biopsy (or fat pad aspirate) for amyloid (if suspected)
  • quantification of non-isotypic immunoglobulins
  • skeletal survey

Special tests indicated in some patients

  • SFLC assay in oligo secretory, light chain only and non secretory disease
  • MRI, CT scan (1)

NICE state (2):

  • imaging for people with suspected myeloma

    • offer imaging to all people with a plasma cell disorder suspected to be myeloma
    • consider whole-body MRI as first-line imaging
    • consider whole-body low-dose CT as first-line imaging if whole-body MRI is unsuitable or the person declines it
    • only consider skeletal survey as first-line imaging if whole-body MRI and whole-body low-dose CT are unsuitable or the person declines them
    • do not use isotope bone scans to identify myeloma-related bone disease in people with a plasma cell disorder suspected to be myeloma

Note that NICE guidance also recommends the use of serum free light chains (SFLC) rather than urinary Bence Jones protein (BJP), and studies have validated this

SFLC replaces BJP in the British Society for Haematology/UK Myeloma Forum Guideline (1)

  • although it is noted that BJP may still be required for some clinical trials

  • urine albumin:creatinine ratio along with troponin and Nterminal pro-B-type natriuretic peptide (NT-proBNP) can be a useful screening tool for detecting amyloid.


  • 1.Sive, J., Cuthill, K., Hunter, H., Kazmi, M., Pratt, G., Smith, D. and (2021), Guidelines on the diagnosis, investigation and initial treatment of myeloma: a British Society for Haematology/UK Myeloma Forum Guideline. Br. J. Haematol., 193: 245-268.
  • 2. NICE (February 2016).Myeloma