Abnormal cellular DNA content, a hallmark of malignancy, is known to be an important prognostic factor in many human solid tumors; however, no data have been published on whether cellular DNA content carries prognostic significance for patients with nasopharyngeal cancer (NPC). Archival, formalin-fixed, paraffin-embedded pathology specimens representing pretreatment tissue biopsies from 55 patients (41 men and 14 women) with NPC were analyzed for cellular DNA content in a retrospective fashion from 1968 to 1988. Individual tumors were classified as either lymphoepithelioma, squamous cell, or anaplastic carcinoma, and were staged according to International Union Against Cancer (UICC) criteria. All patients were treated with curative intent using a 4 to 6 MeV linear accelerator to total doses ranging from 50 to 60 Gy in 4 to 6 weeks. The overall 5-year actuarial survival for all 55 patients was 44.4% (men, 41%; women, 52%). Survival by T stage was as follows: T1, 65%; T2, 51%; T3, 36%; and T4, 27%. Similarly, the 5-year survival rate declined as the bulk of nodal metastases increased: N0, 62%; N2, 50%; N3, 37%; and N1, 25%. Patients who had anaplastic carcinoma had a 5-year survival of 73%, those with lymphoepithelioma had a 60% survival, and those with squamous cell cancer (SCC) had a 30% survival. There was a statistically significant difference in 5-year survival between patients with SCC and those with nonkeratinizing histologies (P less than 0.05). In addition, there was a significant association between patients older than 40 years of age with SCC and patients younger than 40 years of age with nonkeratinizing malignancies (P less than 0.01). Of the 55 tumors successfully analyzed, 22 (40%) were diploid and 33 (60%) were aneuploid. The mean coefficient of variation (CV) of all 55 samples was 6.17%. There was no significant difference in 5-year survival between patients with diploid and those with aneuploid tumors (48% versus 42%). Furthermore, there was no statistically significant survival difference between aneuploid and diploid tumors within any one histologic subgroup. There was also no significant survival difference related to the DNA index. The results indicate that the extent of local tumor spread is still the most important prognostic factor for patients treated with radiotherapy for NPC. The data support the conclusion that patients with lymphoepithelioma and anaplastic carcinomas have a superior survival to patients with squamous cell carcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)