INTRODUCTION: In pathology laboratories, occupational exposure to chemical substances such as formaldehyde (FA) and xylene constitutes  risk factors for genetic damage. FA, a tissue fixative and preservative, is classified as a human carcinogen by the International Agency for Research on Cancer (Group1/IARC) due to the increased incidence of nasopharyngeal cancer and leukemia in occupationally exposed populations. Xylene, a solvent used in tissue clearing and deparaffinization processes of paraffin-embedded samples, is toxic and exhibits neurotoxic properties, in addition to being associated with respiratory disorders. DNA alterations induced by these compounds have not yet been studied in Division of Pathology (DIPAT/INCA) workers who are occupationally exposed, making this an unprecedented study with comet assay (CA) and the micronucleus test (MN). OBJECTIVE: To evaluate occupational exposure to xylene and FA among DIPAT/INCA professionals by analyzing the potential genotoxic effects through the CA and MN in whole blood. METHODS: The Informed Consent Form (ICF) was administered to participants, and sociodemographic data were collected through the REDCap platform. Blood samples were collected and processed from the exposed group (n = 33) and the comparison group (n = 20), considering a total of 45 participants in both groups. DNA damage was evaluated using two genotoxicity methods applied and validated at LabTox: i) Comet Assay (CA): For each sample, 100 cells were analyzed and classified according to the degree of DNA damage, ranging from no damage to extreme damage (“hedgehog” comet); ii) Cytokinesis-block Micronucleus Test (MN): Conducted in lymphocytes to quantify micronuclei (MN), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs) in 2,000 binucleated cells per sample. RESULTS: So far, eight slides per group have been analyzed in the CA and five in the MN, representing preliminary results. In the comet assay, the mean percentage of undamaged cells (class 0) was 99.4% in the exposed group versus 96.9% in controls, while damaged cells (classes 1–4) were 0.23% vs. 2.36%, and “hedgehog” comets 0.46% vs. 0.75%, suggesting greater variability among controls, possibly due to the small sample size. Although there were no active smokers, three passive smokers were identified among controls and one among the exposed, which may also have influenced the results. In the micronucleus test, mean values were 16.2 micronuclei and 17.4 total micronuclei (tMN) in the exposed group, compared to 8.0 and 8.6 tMN in controls, with higher frequencies of nuclear buds (4.8 vs. 2.8) and nucleoplasmic bridges (3.2 vs. 0.2), indicating a trend of greater genotoxic effect among the exposed. The findings suggest higher susceptibility to DNA damage in the exposed group, although further sample analysis is needed. CONCLUSION AND IMPLICATIONS:  This study highlights that occupational risk assessment is essential for surveillance, prevention, and health promotion in cancer-related institutions, requiring continuous evaluation of exposure to carcinogenic compounds to protect workers’ health. Within this framework, the 3Rs concept in occupational safety and health (reduction, replacement, and refinement) guides risk minimization through decreased exposure, adoption of safer alternatives, and improved work practices, including process control, training, appropriate PPE, and health monitoring, thereby promoting safer occupational environments.