This is the final version. Available on open access from Royal College of General Practitioners via the DOI in this recordBACKGROUND: Multiple myeloma is a haematological cancer characterised by numerous non-specific symptoms leading to diagnostic delay in a large proportion of patients. AIM: To identify which blood tests are useful in suggesting or excluding a diagnosis of myeloma. DESIGN AND SETTING: A matched case-control study set in UK primary care using routinely collected data from the Clinical Practice Research Datalink. METHOD: Symptom prevalence and blood tests were analysed up to 5 years before diagnosis in 2703 cases and 12 157 matched controls. Likelihood ratios (LR) were used to classify tests or their combinations as useful rule-in tests (LR+ = ≥5), or rule-out tests (LR- = ≤0.2). RESULTS: Raised plasma viscosity (PV) had an LR+ = 2.0, 95% confidence interval [CI] = 1.7 to 2.3; erythrocyte sedimentation rate (ESR) 1.9, 95% CI = 1.7 to 2.0; and C-reactive protein (CRP) 1.2, 95% CI = 1.1 to 1.4. A normal haemoglobin had an LR- = 0.42, 95% CI = 0.39 to 0.45; calcium LR- = 0.81, 95% CI = 0.78 to 0.83; and creatinine LR- = 0.80, 95% CI = 0.77 to 0.83. The test combination with the lowest LR- was all normal haemoglobin with calcium and PV, which had an LR- = 0.06, 95% CI = 0.02 to 0.18, though the LR- for normal haemoglobin and PV together was 0.12 (95% CI = 0.07 to 0.23). CONCLUSION: Plasma viscosity and ESR are better for both ruling in and ruling out the disease compared with C-reactive protein. A combination of a normal ESR or PV and normal haemoglobin is a simple rule-out approach for patients currently being tested in primary care.This manuscript presents work carried out as part of a DPhil scholarship awarded to Constantinos Koshiaris funded by the Primary Care Research Trust, the University of Oxford, and National Institute for Health Research (NIHR) Oxford CLAHRC. This article presents independent research funded by the NIHR.