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Objective: To develop a simple clinical decision rule that could increase the yield of serum and urine protein electrophoresis (SPE/UPE) without loss of sensitivity.Design: A cross-sectional study of inpatients with a SPE/UPE performed over a 5-year period (2001-2006) with complete data on electrolytes, globulins, full blood count, creatinine, age, and gender.Setting: A tertiary-care general teaching hospital serving the Hunter Valley in New South Wales, with a referral population of over 1 million.Participants: A total of 14,374 adult patients admitted between January 2001-November 2006.Main Outcome Measures: Paraprotein on serum and/or urine protein electrophoresis (SPE/UPE).Results: Five points were assigned for globulin > 41 g/l, 3 points for age > or = 60, 2 points for each of hemoglobin < 121 and male gender, and 1 point for estimated glomerular filtration rate (eGFR) < 60. Total scores of 0-5, 6-10, and > or = 11 corresponded to positive likelihood ratios of an abnormal SPE/UPE of 1, 2.5, and 6.6, respectively. The predictive ability of this model was strong, with an area under the curve of approximately 0.8. Results in the validation set were almost identical.Conclusion: A clinical decision rule using simple clinical variables has the potential to improve the yield of SPE/UPE. This rule however needs to be verified prospectively. [ABSTRACT FROM AUTHOR]