This study aimed at investigating parameters of chemical extraction associated with the detection of mutagenicity in soil samples extracts. In order to evaluate the extraction efficiency of inorganic mutagens, besides the chemical analysis of metals, the Salmonella/microsome assay was performed in the preincubation and microsuspension procedures, using two solvents, and using two extraction methodologies. The efficiency of two organic compound extraction methods was compared by qualitative analysis using CG/MS in Scan mode. The results of the analysis of inorganic extracts correlated with the mutagenicity results. Mutagenic effects were detected only in the acidic extracts of soil that were shaken, in the microsuspension assay, both in the presence and absence of metabolic activation. The other conditions tested demonstrated higher cytotoxicity and negative mutagenic effects. As to the organic compounds, Accelerated Solvent Extraction (ASE) proved more effective than extraction using ultrasound (sonication). This study will help the implementation of extraction parameters to evaluate the presence of mutagenic substances in soil samples, both of inorganic and organic origins, suggesting the implementation of acidic extraction for the assessment of inorganic mutagenicity from soil samples and confirming the efficiency of ASE extraction for the assessment of organic compounds.