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Description: Despite the widespread use of lesion-symptom mapping (LSM) techniques to study associations between location of brain damage and language deficits, the prediction of language deficits from lesion location remains a substantial challenge. The present study examined several factors which may impact lesion-symptom prediction by (1) testing the relative predictive advantage of general language deficit scores compared to composite scores that capture specific deficit types, (2) isolating the relative contribution of lesion location compared to lesion size, and (3) comparing standard voxel-based lesion-symptom mapping (VLSM) with a multivariate method (sparse canonical correlation analysis, SCCAN). Analyses were conducted on data from 128 participants who completed a detailed battery of psycholinguistic tests and underwent structural neuroimaging (MRI or CT) to determine lesion location. For both VLSM and SCCAN, overall aphasia severity (Western Aphasia Battery Aphasia Quotient) and object naming deficits were primarily predicted by lesion size, whereas deficits in Speech Production and Speech Recognition were better predicted by a combination of lesion size and location. The implementation of both VLSM and SCCAN raises important considerations regarding controlling for lesion size in lesion-symptom mapping analyses. These findings suggest that lesion-symptom prediction is more accurate for deficits within neurally-localized cognitive systems when both lesion size and location are considered compared to broad functional deficits, which can be predicted by overall lesion size alone.