This study compares cancer incidence among the Seneca Nation of Indians (SNI) between 1955 and 1984 with cancer incidence patterns exhibited by the general population of New York State (NYS), exclusive of New York City. The cohort for this study consisted of all members of the SNI enrolled on January 1, 1955 and residing in NYS (N = 3262). Cancer incidence among the SNI is compared with cancer incidence patterns in NYS using age and sex standardized incidence ratios (SIR). Decreased cancer incidence was observed for all sites combined with SNI males exhibiting 64% of expected incidence and females exhibiting 53% of expected incidence. Although incidence deficits were observed for several sites, cancer incidence was not significantly elevated for any cancer site. Results from this investigation will contribute to the understanding of patterns of malignant disease among native peoples and aid in directing cancer control programs and services available to native groups.