Carbon monoxide is a toxic gas with potentially lethal action, which forms as a result of incomplete combustion in conditions where there is a lack of oxygen and which, therefore, is present in varying percentages in environments where fire develops. In addition to carbon monoxide, other factors such as cyanide may contribute or might actually be the primary cause of a subject's demise. In cases of exposure to both substances, the role of cyanide as a toxic/lethal agent in death by asphyxiation is still not clear: some authors attribute a primary action to such a gas in causing the demise, others consider carbon monoxide to be the only cause of the lethal event. For this reason it is in the interest of forensic medicine to study all lethal cases of exposure to toxic substances originating from fires of various types of materials, in order to determine information regarding kinetic action and the possible strengthening of the effect of the two substances. Two case studies are presented here, in which the results of the toxicological examinations are quite different, and the contributions of CO and HCN in a fire asphyxiation are considered.