Over the past decade, there have been a rising number of clinically used tests that combine 2 or more biochemical or molecular assays, demographics, and clinical information into an algorithm to generate diagnostic, prognostic, or predictive information for a specific disease. The concept of multianalyte analyses is relatively new in the field of laboratory medicine. Dating back to the 1980s, prenatal screening for fetal abnormalities, such as Down syndrome, by use of maternal biomarkers is among the pioneer tests that use algorithmic analyses for risk assessment. Yet, the number of multianalyte algorithms used clinically remains modest. The American Medical Association provides current procedural terminology (CPT)8 codes for 20 multianalyte assays with algorithmic analyses (MAAAs.) Among these, 9 consist of biochemical markers detected by immunoassay or mass spectrometry, with or without other clinical information; 11 use molecular genetics markers; and 1 is for generic use. In this Q&A, we refer to multivariable tests with risk scores as MAAAs, although not all of them have an associated MAAA CPT code. Generally speaking, MAAAs aim at improving diagnostics for diseases in which single biomarkers have limited clinical validity. The Prostate Health Index (Beckman Coulter) and the 4Kscore® (GenPath) exemplify some of these strategies for prostate cancer detection. Likewise, multianalyte analyses such as the Risk of Ovarian Malignancy Algorithm (ROMA®) and OVA1® and its second-generation OVERATM (Vermillion Inc.) improve upon the suboptimal performance of the tumor marker CA125 in the differential diagnosis and likelihood of ovarian carcinoma in women presenting with a pelvic mass. While both have Food and Drug Administration (FDA) clearance, ROMA is a nonproprietary algorithm cleared on various commercial immunoassays (Fujirebio Diagnostics, Inc.; Abbott Laboratories; Roche Diagnostics). Early identification of acute kidney injury is another area in which an FDA-approved multianalyte test, Nephrocheck® (Astute Medical), …