While it is known that diesel fuel combustion engines produce much lower concentrations of carbon monoxide (CO) than gasoline engines, these emissions could certainly generate lethal ambient concentrations given a sufficient amount of time in an enclosed space and under suitable environmental conditions. The authors report a case of CO poisoning which was initially referred for autopsy as a presumed natural death of a truck driver found in the secure cab of a running diesel tractor trailer truck. Completion of the preliminary investigation ascribed death to complications of ischemic heart disease (IHD), pending toxicological analysis that included quantification of CO. When the toxicology results showed lethal blood COHbg, the cause of death was re-certified as CO intoxication secondary to inhalation of (diesel) vehicular exhaust fumes. Because of the unique source of fatal CO intoxication in this case, the contributory IHD and the possible contaminants in the putrefied blood, a 10-year retrospective review was conducted on all nonfire related CO deaths autopsied (n = 94) at the Office of the Chief Medical Examiner in Louisville, KY from 1994 to 2003. For validation of the COHbg detection method used by the Kentucky Office of Forensic Toxicology (KYOFT), blood samples from these cases along with controls were submitted to three laboratories using various analytical methods yielding no statistically significant differences. Lastly, an extensive literature review produced no scientifically reported cases of fatal CO poisoning attributed to diesel fuel exhaust.