The association between several clinical, histologic and karyometric variables and the survival rates of patients with ampullary carcinoma was examined. Cases were limited to those treated exclusively by pancreaticoduodenectomy for which follow-up data was available, eliminating those cases with deaths due to other causes. The histologic type was classified as papillary, intestinal or mixed while the differentiation was recorded as well, moderate or poor. The stroma was categorized as scanty, moderate or abundant, and the tumor stage was evaluated according to Martin's classification. High-resolution morphometric and microphotometric (DNA content) evaluation of Feulgen-stained nuclei was performed using the microTICAS system. Statistical analyses were performed to examine the relationship between these variables and survival. Neither the tumor stage nor the presence of positive lymph nodes was a significant prognostic indicator, nor was the degree of differentiation or the amount of stroma. However, the survival showed a significant association with several karyometric variables and with the histologic type. Specifically, aneuploid DNA ploidy profiles, higher mean ploidy values and larger nuclei were associated with a lower survival rate. Short-term survivors (less than five years) had a mean ploidy of 2.8N, a mean 5N exceeding rate of 8.3% and a mean nuclear area of 41 sq microns, while long-term survivors (greater than or equal to five years) had corresponding means of 1.9N, 0.6% and 26 sq microns. These differences are all significant at a two-tailed significance level of less than .05 using a separate variance estimate t-test. In addition, papillary tumors showed a better prognosis than did intestinal or mixed tumors (Breslow P less than .04 and Mantel-Cox P less than .009).