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Introduction Nanoscale particles (1-100 nm) may be naturally occurring; intentionally-produced for commercial purposes or unintentionally-produced by manufacturing processes or human activities. Toxicological data have suggested a possible carcinogenic effect of nanoscale particles and have shown that they have the ability to translocate into different organs including the brain. While epidemiological data on nanoscale particles are very scarce to date, there is some suggestion of their potential role in cancer (e.g. diesel exhaust emissions classified as carcinogenic for humans by IARC). The objective of this study was to estimate the association between occupational exposure to nanoscale particles and risk of brain tumour in adults. Methods The CERENAT study is a multicenter case-control study carried out in four districts of France between 2004 and 2006. From detailed occupational histories, occupational exposure to unintentionally-produced nanoscale particles was retrospectively assessed by the MatPUF job exposure matrix providing a probability and frequency of exposure for each combination occupation × industry according to international and national classifications. Conditional logistic regression was used to estimate ORs and 95% CIs. Results Overall, 596 brain tumour cases and 1192 matched controls were included in this study. Among men, a significant association between occupational exposure to nanoscale particles and brain tumour was observed (OR = 1.5; 95% CI: 1.1–2.2). This increased OR was essentially observed in the highest exposure categories (OR = 1.6; 95% CI: 1.1–2.4 for a total duration of exposure over 30 years) as well as for carbonaceous (OR = 1.5; 95% CI: 1.1–2.3) and HAP nanoscale particles (OR = 1.6; 95% CI: 1.1–2.4). Conclusion Even if these preliminary results should be confirmed by other analyses including the intensity of exposure (on-going work in a further version of the job-exposure matrix), these results should encourage further epidemiological research on nanoscale particles.