Cateura landfill located in Asuncion-Paraguay is the site of final disposal of tons of garbage of all kinds coming from urban, industrial and commercial areas. Due to an inadequate waste management system, there is a big concern in our country on how it can affect people working within the landfill as waste pickers. When a high risk of exposure affecting workers in their work places is supposed, defining biomarkers of genotoxic damage is obligatory. The principal aim of this study was to evaluate the genetic damage in occupationally exposed women in their work environments through two established biomarkers: the single-cell gel electrophoresis assay (SCGE) accomplished in peripheral blood and the micronucleus test performed in exfoliated cells from oral mucosa (BMCyT). This is an analytical observational cohort study involving 50 women occupationally exposed and 34 unexposed women. A statistically significant increase (p < 0.05) in the parameters to measure genotoxicity was observed in the garbage recyclers of the landfill, compared to the control group. The frequency of Micronuclei (MN) and other nuclear abnormalities such as karyolytic and karyorrhectic cells were higher in exposed women. In addition, significant differences in the % of DNA in the tail of comets between exposed and control groups were found. Our results suggest that the increase in DNA damage and nuclear alterations found in exposed-waste pickers women can be explained as a result to their direct contact with chemicals, many of them identified as genotoxic and other alleged mutagens. This chronic exposure could be diminished by using safety procedures and suitable personal protective equipment inside the workplace. The burden of morbidity due to occupational exposure to genotoxic agents in this place is unknown, therefore, these types of studies should be addressed in order to advice to authorities on social policies of protection of landfills workers.