In burnt or skeletonized bodies dental hard tissue sometimes is the only remaining specimen available. Therefore, it could be used as an alternative matrix in post mortem toxicology. Additionally, analysis of dental tissues could provide a unique retrospective window of detection. For forensic interpretation, routes and rates of incorporation of different drugs as well as physicochemical differences between tooth root, tooth crown and carious material have to be taken into account. In a pilot study, one post mortem tooth each from three drug users was analyzed for medicinal and illicit drugs. The pulp was removed in two cases; in one case the tooth was root canal treated. The teeth were separated into root, crown and carious material and drugs were extracted from the powdered material with methanol under ultrasonication. The extracts were screened for drugs by LC-MS(n) (ToxTyper™) and quantitatively analyzed with LC-ESI-MS/MS in MRM mode. The findings were compared to the analytical results for cardiac blood, femoral blood, urine, stomach content and hair. In dental hard tissues, 11 drugs (amphetamine, MDMA, morphine, codeine, norcodeine, methadone, EDDP, fentanyl, tramadol, diazepam, nordazepam, and promethazine) could be detected and concentrations ranged from approximately 0.13pg/mg to 2,400pg/mg. The concentrations declined in the following order: carious material>root>crown. Only the root canal treated tooth showed higher concentrations in the crown than in the root. In post mortem toxicology, dental hard tissue could be a useful alternative matrix facilitating a more differentiated consideration of drug consumption patterns, as the window of detection seems to overlap those for body fluids and hair.