Abstract Background Formaldehyde (FA) is a human carcinogen. It is commonly used in diluted form as formalin. The purpose of this work was to evaluate the frequencies of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) as a consequence of the exposure to FA in a hospital setting, taking into account the role of some polymorphisms in developing genotoxic damage. Methods CAs and SCEs assays were performed on peripheral blood lymphocytes of 57 pathologists enrolled in Turin hospitals (Italy) and 48 unexposed enrolled as controls. All subjects were genotyped for CYP1A1 exon 7 (A>G), CYP1A1*2A (T>C), CYP2C19*2 (G>A), GSTT1 (Positive/Null), GSTM1 (Positive/null), GSTP1 (A>G), XRCC1 (G399A), XRCC1 (C194T), XRCC1 (A280G), XPD (A751C), XPC exon 15 (A939C), XPC exon 9 (C499T), TNFα -308 (G>A), IL10 -1082 (G>A), IL10 -819 (C>T) and IL6 -174 (G>C) gene polymorphisms. Due to the little number of recessive homozygotes, we compared the dominant genotype with the combined group of heterozygotes and recessive homozygotes. Results Among pathologists, the mean value of personal air-FA was 64.2 µg/m3, mean significantly higher (p = 0.000) than controls (19.1 µg/m3). Similarly, pathologists showed significantly higher values of SCEs (p = 0.009) and CAs (p = 0.000) with respect to controls. In the same group, CYP2C19*2 (p = 0.011), XRCC1 (G399A) (p = 0.007), and IL10 (-1082) (p = 0.042) gene polymorphisms influenced the CAS levels, as well as those of CYP1A1 exon 7 (p = 0.010), XPD A751C (p = 0.002), XPC C499T (p = 0.040), and IL10 (-819) (p = 0.005) the levels of SCEs. In control group, CAs resulted significantly lower in CYP1A1 exon 7 dominant homozygotes (p = 0.001). Conclusions Our study confirms the role of FA as an inductor of genotoxicity, even when, daily, workers are exposed to low FA levels. Some genetic polymorphisms seem to have an influence in modulating the effect of FA exposure, highlighting, in occupational health studies, the role of the individual susceptibility. Key messages FA exposure is confirmed to be a genotoxicity inductor even at low concentrations. Some genetic polymorphisms seem to have a role in the modulation of FA exposure-related damage.