Cadmium is a toxic heavy metal naturally absorbed and accumulated by plants. It is present in tobacco (Nicotiana tabacum) leaves and potentially in the smoke of cigarettes. Reducing the cadmium content in leaves of tobacco plants requires a better understanding of the mechanisms controlling the accumulation of this element. Our project aims at identifying genetic loci controlling cadmium accumulation using two approaches, a genome wide association study (GWAS) and a quantitative trait loci (QTL) approach. The GWAS approach was developed on a panel of ~160 ancient varieties, using ~6000 single-nucleotide polymorphisms (SNPs). The QTL approach was developed on a F2 progeny issued from a cross between two lines showing a two-fold variation in leaf cadmium content. This QTL approach was done using a Bulk Segregant Analysis (BSA) with ~8000 SNP markers generated by double-digest Restriction Associated DNA (ddRAD) sequencing. For both approaches the phenotyping was done in the field. The GWAS approach revealed different markers associated to the change in cadmium accumulation but still remain limited by the number of markers. In contrast the QTL approach revealed ~70 SNPs arranged at least three loci controlling cadmium content in tobacco leaves. These loci are under further examination. Our results may help breeders to create new tobacco varieties with reduced cadmium contents in their leaves.