We examined the relationships among nuclear DNA content, tumor origin, nuclear size, and prognosis in squamous cell lung cancer. Central tumors had significantly higher DNA aneuploidy (83%, p<0.01) and DNA indices (1.65+/-0.40, p<0.01) than did peripheral tumors (40%, 1.29+/-0.37, respectively). All six women in the study (five no smokers) had peripheral diploid tumors. Patients (15) with diploid tumors had significantly longer survival times (a 5-year survival rate of 63%) than did those (28) with aneuploid tumors (29%, p<0.01). Patients with tumors having both large nuclei (nuclei greater than 11 mum in mean diameter) and a DNA index of 1.0 had the longest survival times (a 5-year survival rate of 100%). This was followed by patients with large-nucleus tumors and a DNA index of more than 1.51 (71%). However, all patients with small-nucleus tumors (tumors with nuclei less than 10 mum in mean diameter) and a DNA index of more than 1.51 died within 30 months. These results suggested that the malignancy level of squamous cell lung cancer and the prognosis could be determined by studying the DNA content and the size of the tumor nuclei, and that there may be differences in the pathogenesis and/or malignancy of central and peripheral tumors.