Purpose. The purpose of this study was to investigate the effect of the presence of atypical birefringence patterns, as measured by the typical scan score (TSS), on the diagnostic accuracy of a scanning laser polarimeter (the GDx VCC; Carl Zeiss Meditec, Inc., Dublin, CA) assessed by receiver operating characteristic (ROC) curves for discriminating between glaucoma and healthy eyes. methods. Two hundred thirty-three glaucomatous eyes (repeatable abnormal visual fields by pattern standard deviation [PSD] and/or glaucoma hemifield test [GHT]) from 153 patients with glaucoma and 104 eyes from 71 healthy participants enrolled in the UCSD Diagnostic Innovations in Glaucoma Study (DIGS) were imaged using the GDx VCC. An ROC regression model was used to evaluate the influence of the covariates TSS; disease severity, defined as standard automated perimetry (SAP) mean deviation [MD]; and age in years on the diagnostic accuracy of the GDx parameters nerve fiber indicator [NFI], TSNIT (temporal, superior, nasal, inferior, temporal) average thickness, superior average thickness, inferior average thickness, and TSNIT standard deviation. Areas under the ROC curve were calculated for specific levels of the covariates according to the results provided by the model. results. TSS and SAP MD significantly affected the diagnostic accuracy of each investigated GDx VCC parameter. Low TSSs, indicating the presence of atypical scans, were associated with decreased accuracy. For NFI, ROC curve areas ranged from 0.749 (when TSS = 20) to 0.904 (when TSS = 100). A similar influence of TSS was found for other parameters. In addition, diagnostic accuracy increased with increasing disease severity. For instance, for NFI, ROC curve areas ranged from 0.853 (when SAP MD = −3) to 0.954 (when SAP MD = −15). conclusions. The diagnostic accuracy of GDx VCC parameters is affected by disease severity and is adversely affected by the presence of atypical retardation patterns (i.e., decreasing TSS). GDx VCC scans with atypical scan patterns should be interpreted with caution when used in clinical practice.