Objective and background Frontotemporal dementia (FTD) is a common, non-Alzheimer's dementia. Its familial occurrence has been reported, but the frequency of positive family history is unknown. Methods We carried out a nationwide genetic-epidemiologic study of FTD in the Dutch population of 15 million people. The family history of dementia was analyzed in 74 FTD patients and 561 age- and gender-matched control subjects. Results We found one or more first-degree relatives with dementia before age 80 in 38% (28 of 74) of FTD patients, but only in 15% (84 of 561) of control subjects. Ten percent of FTD patients had two or more first-degree relatives with dementia compared with 0.9% of the control subjects. Seven percent of FTD patients showed the ApoE4E4 genotype versus 2.3% of the control subjects. The first-degree relatives of FTD had a risk of 22% for dementia before age 80 compared with 11% in relatives of control subjects. The age of onset of dementia in affected first-degree relatives of FTD patients (60.9 ± 10.6 years) was significantly lower than among affected relatives of control subjects (72.3 ± 8.5 years). The first-degree relatives of FTD patients were 3.5 times (95% CI, 2.4 to 5.2) more at risk for developing dementia before age 80 than relatives of control subjects. The hazard ratio in the subgroup with unknown linkage to chromosome 17 was 2.4 (95% CI, 1.5 to 3.7). Conclusion This study documents the importance of genetic factors in a proportion of FTD patients with the age at onset of dementia in first-degree relatives being 11 years earlier than in the general population.