Previous studies that measured brain activity in frontotemporal dementia (FTD) used univariate analyses, examining each region of interest separately. We explored in a multicenter European research program the principal brain clusters characterized by a common variability in cerebral metabolism in FTD. Seventy patients with frontal variant (fv) FTD were selected according to international clinical recommendations; principal component analysis (PCA) was performed on FDG-PET metabolic images, looking for covariance clusters in this large population. A first metabolic cluster included most of the lateral and medial prefrontal cortex, bilaterally; PC1 scores correlated with performances on memory and executive neuropsychological tasks. Moreover, FDG-PET images in fv-FTD were further characterized by a metabolic covariance in two clusters comprising the subcallosal medial frontal region, the temporal pole, medial temporal structures and the striatum, separately in the left and in the right hemisphere. The study provides original data-driven arguments for metabolic involvement of separate brain clusters in the rostral limbic system, corresponding to pathological poles differentially affected in each FTD patient.