ABSTRACT: Purpose:This manuscript examines shifts in patterns of cancer incidence among the Seneca Nation of Indians (SNI) for the interval 1955-1969 compared to 1990-2004. Methods: A retrospective cohort design was used to examine cancer incidence among the SNI during 2 time intervals: 1955-1969 and 1990-2004. Person-years at risk were multiplied by cancer incidence rates for New York State, exclusive of New York City, over 5-year intervals. A computer-aided match with the New York State Cancer Registry was used to identify incident cancers. Overall and site-specific standardized incidence ratios (SIRs = observed/expected × 100), and 95% confidence intervals (CIs), were calculated for both time periods. Results: During the earlier interval, deficits in overall cancer incidence were noted among males (SIR = 56, CI 36-82) and females (SIR = 71, CI 50-98), and for female breast cancers (SIR = 21, CI 4-62). During the more recent intervals, deficits in overall cancer incidence persisted among both genders (males SIR = 63, CI 52-77; females SIR = 67, CI 55-80). Deficits were also noted among males for cancers of the lung (SIR = 60, CI 33-98), prostate (SIR = 51, CI = 33-76) and bladder (SIR = 17, CI = 2–61) and among females for breast (SIR = 33, CI = 20-53) and uterus (SIR = 36, CI = 10-92). No cancer sites demonstrated increased incidence. Persons ages 60-69 years, 70-79 years, and ages 80+ years tended to exhibit deficits in overall incidence. Conclusions: Despite marked changes over time, deficits in overall cancer incidence have persisted between the time intervals studied. Tribal-specific cancer data are important for the development and implementation of comprehensive cancer control plans which align with local needs.