Background: The Symbol Digit Modalities Test (SDMT) is a common screen of cognitive function for people with Multiple Sclerosis (pwMS) but growing acknowledgement that people with cognitive impairment are a heterogeneous population suggests that a single screen may provide limited information. Objective: To assess the adequacy of the SDMT in capturing impairment across specific cognitive domains as measured by a multi-domain cognitive assessment battery (CAB, NeuroTrax). Methods: 113 pwMS were assessed with SDMT and the CAB. Cognitive impairment in each CAB domain was defined as ≥1.5 SD below the normalized mean. Logistic regression models were fit for each CAB domain with domain-specific cognitive impairment as the outcome and SDMT as the predictor, and a classifier created by selecting cutpoints using the Youden Index. Model performance was assessed by predicting domain-specific cognitive impairment in an independent data set consisting of 81 pwMS. Results: SDMT was a significant predictor of cognitive impairment in all outcomes considered (Odds Ratio: 0.885-0.950), but prediction metrics such as area under the receiver operating curve (AUC) were modest (0.623-0.778), and the alignment between observed/predicted impairment was less than optimal. Conclusion: The SDMT is not sufficient to differentiate between impaired and non-impaired pwMS across several cognitive domains.