In the rare case of a male patient presenting with a combined small cell lung carcinoma (SCLC), large cell neuroendocrine carcinoma and adenocarcinoma, we used whole genome analysis by tiling-path array comparative genomic hybridization to evaluate the clonal relationship between nodules. In two areas of SCLC distinguishable by divergent neuroendocrine marker expression (CD56 and chromogranin-A), the presence of identical genomic breakpoints and rearrangements indicated a common origin, with the presence of additional distinct genomic alterations in these two components indicating diverging clonal evolution. The absence of shared genome alteration features for the adenocarcinoma and large cell neuroendocrine carcinoma components suggested that these tumors evolved independently from the SCLC. Taken together, the array comparative genomic hybridization data demonstrate the development and evolution of three independent primary lung cancers in close proximity to each other to form a combined carcinoma. Application of whole genome analysis shows the potential utility of high resolution molecular tools in resolving the origin and delineating the clonal relationships of a tumor that contains heterogeneous histologic components leading to an ambiguous histogenesis.