A unified hypothesis states that the major proximate and ultimate carcinogens of 6-methylbenzo[a]pyrene and benzo[a]pyrene are the metabolites 6-hydroxymethylbenzo[a]pyrene and its sulfate ester, and that representative 6-methylbenzo[a]pyrene derivatives with structural type ArCH₂X are active, whereas benzo[a]pyrene derivatives with structural type ArX are not. Using the methods of synthetic and biological chemistry, aided by the necessary tests for carcinogenic activity, the unified hypothesis was tested. The first step in carcinogenesis by unmethylated benzo[a]pyrene is methylation by SAM-dependent methyltransferases, most favorably in its highly reactive meso-region position. The second is methyl-hydroxylation by oxidases or one-electron oxidation followed by esterification with PAPS-dependent sulfotransferase. Presently, there are strong advocates for the hypothesis that the proximate carcinogens of 6-methylbenzo[a]pyrene and benzo[a]pyrene are not the same. This has led to the conclusion that there may be one mechanism for 6-methylbenzo[a]pyrene and three or more different mechanisms for benzo[a]pyrene. In any case, multiple mechanisms of hydrocarbon carcinogenesis have been proposed. The purpose of this paper is to show that there is strong evidence that a 6-hydroxymethyl sulfate ester is a major ultimate carcinogen of 6-methylbenzo[a]pyrene and benzo[a]pyrene and that a number of representative derivatives of 6-methylbenzo[a]pyrene with structural type ArCH₂X are strongly carcinogenic and capable of generating benzylic carbocations, whereas derivatives of benzo[a]pyrene with structural type ArX that block methyl-substitution are inactive. Relationships between carcinogenic activity and molecular structure of known or potential metabolites and derivatives of 6-methylbenzo[a]pyrene and benzo[a]pyrene have been established. In conclusion, the unified hypothesis is not disproved by the absence of convincing evidence for strong carcinogenic activity of possible intermediates and metabolic end-products that include radical-cation intermediates, terminal ring trans-dihydrodiol, diol-epoxide, and quinone derivatives of 6-methylbenzo[a]pyrene and benzo[a]pyrene. The available evidence shows that benzo[a]pyrene is methylated and 6-methylbenzo[a]pyrene derivatives with structural type ArCH₂X are active, whereas representative unmethylated benzo[a]pyrene derivatives are carcinogenically inert.