Adenocarcinoma (AdC) of the lung represents a common histologic subtype of non-small cell lung cancer. While there is a rising incidence of AdC in nonsmoking women, information on the cytogenetic changes involved has been minimal to date. In the present study, spectral karyotyping analysis uncovered the genome-wide chromosomal aberrations in two AdC tumors derived from women who were lifelong nonsmokers. Simple and complex structural rearrangements were indicated. A ploidy status of hypertetraploidy was suggested in both cases, with recurring derivative translocations involving chromosome arms 3q, 8q, 12q, 15q, 22q, and Xq.