Significant racial disparities in cancer mortality are seen between Medicare beneficiaries. A randomized controlled trial tested the use of lay navigators (care managers) to increase cancer screening of Asian and Pacific Islander Medicare beneficiaries. The study setting was Moloka‘i General Hospital on the island of Moloka‘i, Hawai‘i, which was one of six sites participating in the Cancer Prevention and Treatment Demonstration sponsored by the Centers for Medicare and Medicaid Services. Between 2006 and 2009, 488 Medicare beneficiaries (45% Hawaiian, 35% Filipino, 11% Japanese, 8% other) were randomized to have a navigator help them access cancer screening services (experimental condition, n = 242) or cancer education (control condition, n = 246). Self-reported data on screening participation were collected at baseline and exit from the study, and differences were tested using chi-square. Groups were similar in demographic characteristics and baseline screening prevalence of breast, cervical, prostate, and colorectal cancers. At study exit, 57.0% of women in the experimental arm and 36.4% of controls had had a Papanicolaou test in the past 24 months (P = .001), 61.7% of women in the experimental arm and 42.4% of controls had had a mammogram in the past 12 months (P = .003), 54.4% of men in the experimental arm and 36.0% of controls had had a prostate-specific antigen test in the past 12 months (P = .008), and 43.0% of both sexes in the experimental arm and 27.2% of controls had had a flexible sigmoidoscopy or colonoscopy in the past 5 years (P < .001). Findings suggest that navigation services can increase cancer screening in Medicare beneficiaries in groups with significant disparities.