ABSTRACT: Context: Composed of all or a portion of 13 states, Appalachia is a heterogeneous, economically disadvantaged region of the eastern United States. While mortality from cancer in Appalachia has previously been reported to be elevated, rates of cancer incidence in Appalachia remain unreported. Purpose: To estimate Appalachian cancer incidence by stage and site and to determine if incidence was greater than that in the United States. Methods: Using 1994–1998 data from the central registries of Kentucky, Pennsylvania, and West Virginia, age-adjusted incidence rates were calculated for the rural and nonrural regions of Appalachia. These state rates were compared to rates from the Surveillance, Epidemiology, and End Results (SEER) program for the same years by calculating the adjusted rate ratio (RR) and a 95% confidence interval (CI). Findings: Both the entire and rural Appalachian regions had an adjusted incidence rate for all cancer sites similar to the SEER rate (RR = 1.00 [95% CI, 1.00–1.01] and RR=0.99 [95% CI, 0.99–1.00], respectively). However, incidence of cancer of the lung/ bronchus, colon, rectum, and cervix in Appalachia was significantly elevated (RR = 1.22 [95% CI, 1.20–1.23], 1.13 [95% CI, 1.11–1.14], 1.19 [95% CI, 1.16–1.22], and 1.12 [95% CI, 1.07–1.17], respectively). Incidence of cancer of the lung/bronchus and cervix in rural Appalachia was even more elevated (RR = 1.34 [95% CI, 1.31–1.36] and 1.29 [95% CI, 1.21–1.38], respectively). Incidence of unstaged disease for all cancer sites in Appalachia (RR=1.06 [95% CI, 1.05–1.08]), particularly rural Appalachia (RR = 1.28 [95%CI, 1.25–1.30]), was elevated. Conclusions: Cancer incidence in Appalachia was not found to be elevated. However, incidence of cancer of the lung/bronchus, colon, rectum, and cervix was elevated in Appalachia. The rates of unstaged cancer of every examined site were elevated in rural Appalachia, suggesting a lack of access to cancer health care.