In aphasia due to stroke, language-related activity shifts not only to undamaged cortex within the dominant hemisphere but also toward right-sided areas homotopical to the left-sided lesion. We examined whether a rightward shift takes place in primary progressive aphasia (PPA). Nineteen PPA patients participated, 19 healthy subjects and 14 patients with amnestic mild cognitive impairment who served as controls. Subjects underwent neuropsychological assessment, structural magnetic resonance imaging (MRI), and a functional MRI with a factorial design: words versus pictures and associative-semantic versus visuoperceptual task. Measures of neuropsychological performance were entered as regressors into a multiple linear regression analysis, with response amplitude during the associative-semantic versus control conditions as outcome variable. Language competence correlated negatively with responses in the right anterior temporal cortex and positively with volume and responses in the left-sided homotope. In normal subjects, anterior temporal activation was more extensive to the left than the right (laterality index [LI], +0.64; standard error [SE], 0.11). Laterality was inverted in PPA with word comprehension deficit (LI, - 0.34; SE, 0.19), with an intermediate pattern in PPA without comprehension deficit (LI, +0.23; SE, 0.14). The rightward laterality shift previously reported in aphasic stroke extends to PPA, in particular, when comprehension is deficient.